Doxorubicin

Identification

Summary

Doxorubicin is a medication used to treat various cancers, including AIDS-associated Kaposi's Sarcoma and metastatic cancers.

Brand Names
Adriamycin, Doxil, Myocet
Generic Name
Doxorubicin
DrugBank Accession Number
DB00997
Background

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970.3,39,31 Although they both have aglyconic and sugar moieties, doxorubicin's side chain terminates with a primary alcohol group compared to the methyl group of daunorubicin.39 Although its detailed molecular mechanisms have yet to be understood, doxorubicin is generally thought to exert its effect through DNA intercalation, which eventually leads to DNA damage and the generation of reactive oxygen species.31 Thanks to its efficacy and broad effect, doxorubicin was approved by the FDA in 1974 to treat a variety of cancer, including but not limited to breast, lung, gastric, ovarian, thyroid, non-Hodgkin’s and Hodgkin’s lymphoma, multiple myeloma, sarcoma, and pediatric cancers.1,31,42 However, one of the major side effects of doxorubicin is cardiotoxicity, which excludes patients with poor heart function and requires treatment termination once the maximally tolerated cumulative dose is reached.40

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 543.5193
Monoisotopic: 543.174060775
Chemical Formula
C27H29NO11
Synonyms
  • (1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
  • (8S-cis)-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
  • 14-hydroxydaunomycin
  • 14-hydroxydaunorubicine
  • Doxorubicin
  • Doxorubicin nanoparticles
  • Doxorubicina
  • Doxorubicine
  • Doxorubicinum
  • Hydroxydaunorubicin
  • MTC-DOX
  • MTC-DOX for Injection

Pharmacology

Indication

Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma.42 Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.42 For the liposomal formulation, doxorubicin is indicated for the treatment of ovarian cancer that has progressed or recurred after platinum-based chemotherapy, AIDS-Related Kaposi's Sarcoma after the failure of prior systemic chemotherapy or intolerance to such therapy, and multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.41

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAids-related kaposi's sarcoma•••••••••••••••••••• •••••••• •••••••••• •••• •••••••••• ••••• •••• •••• •• ••••• •• •••••••••••••••••• •••••••••
Treatment ofAids-related kaposi's sarcoma••••••••••••••••••• •• •• ••••• ••• ••••• •••••••• •••••••• •••••••••• •• ••••••••••• •• ••••• •••••••••••••••••• •••••••••• •••••••••• ••••••••••• •••••••••
Treatment ofAcute lymphoblastic leukemia (all)•••••••••••••••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••
Treatment ofAcute myeloid leukemia•••••••••••••••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••
Used in combination to treatAdvanced endometrial cancerRegimen in combination with: Cisplatin (DB00515)••• •••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic.2,37 It is generally thought to exert its antitumor effect by destabilizing DNA structures through intercalation, thus introducing DNA strand breakages and damages.34,35,37 Not only does it alter the transcriptomes of the cells, failure in repairing DNA structures can also initiate the apoptotic pathways.37,38 Additionally, doxorubicin intercalation can also interfere with vital enzyme activity, such as topoisomerase II, DNA polymerase, and RNA polymerase, leading to cell cycle arrests.37 Finally, doxorubicin can also generate cytotoxic reactive oxygen species to exert cellular damages.29

Mechanism of action

Generally, doxorubicin is thought to exert its antineoplastic activity through 2 primary mechanisms: intercalation into DNA and disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages.31

Doxorubicin can intercalate into DNA through the anthraquinone ring, which stabilizes the complex by forming hydrogen bonds with DNA bases.33 Intercalation of doxorubicin can introduce torsional stress into the polynucleotide structure, thus destabilizing nucleosome structures and leading to nucleosome eviction and replacement.34,35 Additionally, the doxorubicin-DNA complex can interfere with topoisomerase II enzyme activity by preventing relegation of topoisomerase-mediated DNA breaks, thus inhibiting replication and transcription and inducing apoptosis.36,37

Moreover, doxorubicin can be metabolized by microsomal NADPH-cytochrome P-450 reductase into a semiquinone radical, which can be reoxidized in the presence of oxygen to form oxygen radicals.7,29 Reactive oxygen species have been known to cause cellular damage through various mechanisms, including lipid peroxidation and membrane damage, DNA damage, oxidative stress, and apoptosis.32 Although free radicals generated from this pathway can be deactivated by catalase and superoxide dismutase, tumor and myocardial cells tend to lack these enzymes, thus explaining doxorubicin's effectiveness against cancer cells and tendency to cause cardiotoxicity.7,29,6

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Humans
ADNA
intercalation
Humans
UNucleolar and coiled-body phosphoprotein 1Not AvailableHumans
ADNA topoisomerase 1
inhibitor
Humans
ADNA topoisomerase 2-beta
inhibitor
Humans
Absorption

Following a 10 mg/m2 administration of liposomal doxorubicin in patients with AIDS-related Kaposi's Sarcoma, the Cmax and AUC values were calculated to be 4.12 ± 0.215 μg/mL and 277 ± 32.9 μg/mL•h respectively.41

Volume of distribution

The steady-state distribution volume of doxorubicin ranges from 809 L/m2 to 1214 L/m2.42

Protein binding

The binding of doxorubicin and its major metabolite, doxorubicinol, to plasma proteins is 75% and is independent of plasma concentration of doxorubicin up to 1.1 µg/mL. Doxorubicin does not cross the blood-brain barrier.42 Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined.41

Metabolism

Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged.6

The two-electron reduction is the major metabolic pathway of doxorubicin.6 In this pathway, doxorubicin is reduced to doxorubicinol, a secondary alcohol, by various enzymes, including Alcohol dehydrogenase [NADP(+)], Carbonyl reductase NADPH 1, Carbonyl reductase NADPH 3, and Aldo-keto reductase family 1 member C3.19,20,6,21,22

The one-electron reduction is facilitated by several oxidoreductase, both cytosolic and mitochondrial, to form a doxirubicin-semiquinone radical.7 These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases.23,24,25,26,27,28 This semiquinone metabolite can be re-oxidized to doxorubicin, although with the concurrent formation of reactive oxygen species (ROS) and hydrogen peroxide.29 It is the ROS generating through this pathway that contributes most to the doxorubicin-related adverse effects, particularly cardiotoxicity, rather than through doxorubicin semiquinone formation.30

Deglycosidation is a minor metabolic pathway, since it only accounts for 1 to 2% of doxorubicin metabolism.6,15 Under the catalysis of cytoplasmic NADPH quinone dehydrogenase, xanthine oxidase, NADPH-cytochrome P450 reductase, doxorubicin can either be reduced to doxorubicin deoxyaglycone or hydrolyzed to doxorubicin hydroxyaglycone.16,17,18

Hover over products below to view reaction partners

Route of elimination

Approximately 40% of the dose appears in the bile in 5 days, while only 5% to 12% of the drug and its metabolites appear in the urine during the same time period. In urine, <3% of the dose was recovered as doxorubicinol over 7 days.42

Half-life

The terminal half-life of doxorubicin ranges from 20 hours to 48 hours.42 The distribution half-life of doxorubicin is approximately 5 minutes.42 For the liposomal formulation, the first-phase and second-phase half-lives were calculated to be 4.7 ± 1.1 and 52.3 ± 5.6 hours respectively for a 10 mg/m2 of doxorubicin in patients with AIDS-Related Kaposi’s Sarcoma.41

Clearance

The plasma clearance of doxorubicin ranges from 324 mL/min/m2 to 809 mL/min/m2 by metabolism and biliary excretion.42 Sexual differences in doxorubicin were also observed, with men having a higher clearance compared to women (1088 mL/min/m2 versus 433 mL/min/m2).42 Following the administration of doses ranging from 10 mg/m2 to 75 mg/m2 of doxorubicin hydrochloride, the plasma clearance was estimated to be 1540 mL/min/m2 in children greater than 2 years of age and 813 mL/min/m2 in infants younger than 2 years of age.42

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Doxorubicin hydrochloride treatment can increase the risk of secondary malignancies based on postmarketing reports. Doxorubicin hydrochloride was mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay.42

Doxorubicin hydrochloride decreased fertility in female rats at doses of 0.05 and 0.2 mg/kg/day (approximately 0.005 and 0.02 times the recommended human dose, based on body surface area).42 In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment.42

A single intravenous dose of 0.1 mg/kg doxorubicin hydrochloride (approximately 0.01 times the recommended human dose based on body surface area) was toxic to male reproductive organs in animal studies, producing testicular atrophy, diffuse degeneration of the seminiferous tubules, and oligospermia/hypospermia in rats. Doxorubicin hydrochloride induces DNA damage in rabbit spermatozoa and dominant lethal mutations in mice.42

Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2. Advise pregnant women of the potential risk to a fetus.42

Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary.42

Pathways
PathwayCategory
Doxorubicin Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Retinoic acid receptor gamma---(C;C) / (C;T)C>TADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.Details
Solute carrier family 28 member 3---(A;A) / (A;G)G > AADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.Details
UDP-glucuronosyltransferase 1-6UGT1A6*4(T;T) / (G;T)G > TADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with doxorubicin.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Doxorubicin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Doxorubicin can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Doxorubicin.
AbirateroneThe serum concentration of Doxorubicin can be increased when it is combined with Abiraterone.
Food Interactions
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of doxorubicin.
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of doxorubicin.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Doxorubicin citrateAJQ2ZNG2WL111266-55-8INEKNBHAPBIAFK-RUELKSSGSA-N
Doxorubicin hydrochloride82F2G7BL4E25316-40-9MWWSFMDVAYGXBV-RUELKSSGSA-N
International/Other Brands
Adriablastina (Pfizer) / Adriblastin (Actavis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Adriamycin PFSSolution2 mg / mLIntravenous; IntravesicalPfizer Canada Ulc1995-12-31Not applicableCanada flag
Adriamycin RdfPowder, for solution10 mg / vialIntravenousPfizer Canada Ulc1996-12-312006-08-02Canada flag
Adriamycin RdfPowder, for solution150 mg / vialIntravenousPfizer Canada Ulc1996-12-312006-08-02Canada flag
Adriamycin RdfPowder, for solution50 mg / vialIntravenousPfizer Canada Ulc1995-12-312006-08-02Canada flag
Adriamycin Rdf Inj 10mg/vialPowder, for solution10 mg / vialIntravenousCarlo Erba Farmitalia Spa1976-12-311996-09-10Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1996-05-01Not applicableUS flag
AdriamycinInjection, powder, lyophilized, for solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Doxorubicin HydrochlorideDoxorubicin hydrochloride (2 mg/1mL)Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous; IntravesicalHospira, Inc.2016-04-182017-12-31US flag
doxorubicin hydrochloride, LiposomalDoxorubicin hydrochloride (2 mg/1mL)Injection, suspension, liposomalIntravenousBaxter Healthcare Corporation2023-12-19Not applicableUS flag
LipodoxDoxorubicin hydrochloride (2 mg/1mL)Injectable, liposomalIntravenousSun Pharmaceutical Industries, Inc.2012-02-092015-05-29US flag
Lipodox 50Doxorubicin hydrochloride (2 mg/1mL)Injectable, liposomalIntravenousSun Pharmaceutical Industries, Inc.2012-02-092015-05-29US flag

Categories

ATC Codes
L01DB01 — Doxorubicin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Anthracyclines
Sub Class
Not Available
Direct Parent
Anthracyclines
Alternative Parents
Tetracenequinones / Aminoglycosides / Anthraquinones / Hexoses / O-glycosyl compounds / Tetralins / Anisoles / Aryl ketones / Alkyl aryl ethers / Oxanes
show 13 more
Substituents
1,2-aminoalcohol / 1,4-anthraquinone / 9,10-anthraquinone / Acetal / Alcohol / Alkyl aryl ether / Alpha-hydroxy ketone / Amine / Amino saccharide / Aminoglycoside core
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinone, anthracycline antibiotic, aminoglycoside, deoxy hexoside, anthracycline (CHEBI:28748) / Other Polyketides, Anthracyclinones (C01661) / Anthracyclinones (LMPK13050001)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
80168379AG
CAS number
23214-92-8
InChI Key
AOJJSUZBOXZQNB-TZSSRYMLSA-N
InChI
InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
IUPAC Name
(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
SMILES
COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O

References

Synthesis Reference

Gian P. Vicario, Sergio Penco, Federico Arcamone, "Daunorubicin and doxorubicin labelled with .sup.14 C at the 14-position and processes for their preparation." U.S. Patent US4211864, issued March, 1976.

US4211864
General References
  1. Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [Article]
  2. Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. [Article]
  3. Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10. [Article]
  4. Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7. [Article]
  5. Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18. [Article]
  6. Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72. [Article]
  7. Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8. [Article]
  8. Quereux G, Marques S, Nguyen JM, Bedane C, D'incan M, Dereure O, Puzenat E, Claudy A, Martin L, Joly P, Delaunay M, Beylot-Barry M, Vabres P, Celerier P, Sasolas B, Grange F, Khammari A, Dreno B: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sezary syndrome. Arch Dermatol. 2008 Jun;144(6):727-33. doi: 10.1001/archderm.144.6.727. [Article]
  9. Ansell SM, Kyle RA, Reeder CB, Fonseca R, Mikhael JR, Morice WG, Bergsagel PL, Buadi FK, Colgan JP, Dingli D, Dispenzieri A, Greipp PR, Habermann TM, Hayman SR, Inwards DJ, Johnston PB, Kumar SK, Lacy MQ, Lust JA, Markovic SN, Micallef IN, Nowakowski GS, Porrata LF, Roy V, Russell SJ, Short KE, Stewart AK, Thompson CA, Witzig TE, Zeldenrust SR, Dalton RJ, Rajkumar SV, Gertz MA: Diagnosis and management of Waldenstrom macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines. Mayo Clin Proc. 2010 Sep;85(9):824-33. doi: 10.4065/mcp.2010.0304. Epub 2010 Aug 11. [Article]
  10. Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC Jr, Creasman W, Yordan E: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985 Apr 15;55(8):1648-53. doi: 10.1002/1097-0142(19850415)55:8<1648::aid-cncr2820550806>3.0.co;2-7. [Article]
  11. Liu W, Yang M, Ping L, Xie Y, Wang X, Zhu J, Song Y: Chemotherapy with a Pegylated Liposomal Doxorubicin-Containing Regimen in Newly Diagnosed Hodgkin Lymphoma Patients. Cardiovasc Toxicol. 2021 Jan;21(1):12-16. doi: 10.1007/s12012-020-09589-z. Epub 2020 Jul 18. [Article]
  12. Yokoi K, Matsuguma H, Nakahara R, Kondo T, Kamiyama Y, Mori K, Miyazawa N: Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol. 2007 Jan;2(1):73-8. doi: 10.1097/JTO.0b013e31802bafc8. [Article]
  13. Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N: Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. doi: 10.1001/jamaoncol.2019.0001. [Article]
  14. Escobar PF, Markman M, Zanotti K, Webster K, Belinson J: Phase 2 trial of pegylated liposomal doxorubicin in advanced endometrial cancer. J Cancer Res Clin Oncol. 2003 Nov;129(11):651-4. doi: 10.1007/s00432-003-0497-8. Epub 2003 Sep 23. [Article]
  15. Licata S, Saponiero A, Mordente A, Minotti G: Doxorubicin metabolism and toxicity in human myocardium: role of cytoplasmic deglycosidation and carbonyl reduction. Chem Res Toxicol. 2000 May;13(5):414-20. doi: 10.1021/tx000013q. [Article]
  16. Lin SR, Lin CS, Chen CC, Tseng FJ, Wu TJ, Weng L, Weng CF: Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells. Mol Cell Biochem. 2020 Dec;475(1-2):119-126. doi: 10.1007/s11010-020-03864-x. Epub 2020 Aug 4. [Article]
  17. Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]
  18. Gutierrez PL, Gee MV, Bachur NR: Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75. [Article]
  19. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
  20. Mordente A, Minotti G, Martorana GE, Silvestrini A, Giardina B, Meucci E: Anthracycline secondary alcohol metabolite formation in human or rabbit heart: biochemical aspects and pharmacologic implications. Biochem Pharmacol. 2003 Sep 15;66(6):989-98. doi: 10.1016/s0006-2952(03)00442-8. [Article]
  21. Bains OS, Karkling MJ, Lubieniecka JM, Grigliatti TA, Reid RE, Riggs KW: Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63. doi: 10.1124/jpet.109.160614. Epub 2009 Dec 9. [Article]
  22. Novotna R, Wsol V, Xiong G, Maser E: Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. doi: 10.1016/j.toxlet.2008.06.858. Epub 2008 Jun 21. [Article]
  23. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  24. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
  25. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]
  26. Gustafson DL, Swanson JD, Pritsos CA: Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. Cancer Commun. 1991 Sep;3(9):299-304. doi: 10.3727/095535491820873038. [Article]
  27. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
  28. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]
  29. Minotti G, Recalcati S, Mordente A, Liberi G, Calafiore AM, Mancuso C, Preziosi P, Cairo G: The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium. FASEB J. 1998 May;12(7):541-52. doi: 10.1096/fasebj.12.7.541. [Article]
  30. Miyamoto Y, Koh YH, Park YS, Fujiwara N, Sakiyama H, Misonou Y, Ookawara T, Suzuki K, Honke K, Taniguchi N: Oxidative stress caused by inactivation of glutathione peroxidase and adaptive responses. Biol Chem. 2003 Apr;384(4):567-74. doi: 10.1515/BC.2003.064. [Article]
  31. Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, Altman RB: Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2011 Jul;21(7):440-6. doi: 10.1097/FPC.0b013e32833ffb56. [Article]
  32. Doroshow JH: Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4514-8. doi: 10.1073/pnas.83.12.4514. [Article]
  33. Chaires JB, Satyanarayana S, Suh D, Fokt I, Przewloka T, Priebe W: Parsing the free energy of anthracycline antibiotic binding to DNA. Biochemistry. 1996 Feb 20;35(7):2047-53. doi: 10.1021/bi952812r. [Article]
  34. Yang F, Kemp CJ, Henikoff S: Doxorubicin enhances nucleosome turnover around promoters. Curr Biol. 2013 May 6;23(9):782-7. doi: 10.1016/j.cub.2013.03.043. Epub 2013 Apr 18. [Article]
  35. Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J: Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun. 2013;4:1908. doi: 10.1038/ncomms2921. [Article]
  36. Jawad B, Poudel L, Podgornik R, Steinmetz NF, Ching WY: Molecular mechanism and binding free energy of doxorubicin intercalation in DNA. Phys Chem Chem Phys. 2019 Feb 13;21(7):3877-3893. doi: 10.1039/c8cp06776g. [Article]
  37. Tacar O, Sriamornsak P, Dass CR: Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013 Feb;65(2):157-70. doi: 10.1111/j.2042-7158.2012.01567.x. Epub 2012 Aug 2. [Article]
  38. Stamm P, Kirmes I, Palmer A, Molitor M, Kvandova M, Kalinovic S, Mihalikova D, Reid G, Wenzel P, Munzel T, Daiber A, Jansen T: Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function. Life Sci. 2021 Nov 1;284:119879. doi: 10.1016/j.lfs.2021.119879. Epub 2021 Aug 11. [Article]
  39. Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI: Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267-85. doi: 10.2174/092986709788803312. Epub 2009 Sep 1. [Article]
  40. van der Zanden SY, Qiao X, Neefjes J: New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J. 2021 Nov;288(21):6095-6111. doi: 10.1111/febs.15583. Epub 2020 Oct 19. [Article]
  41. FDA Approved Drug Products: DOXIL (doxorubicin hydrochloride) liposome injection, for intravenous use [Link]
  42. FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, for intravenous use [Link]
  43. EMA Approved Drug Products: Celdoxome (Doxorubicin hydrochloride) pegylated liposomal for intravenous use [Link]
  44. Doxorubicin Hydrochloride Pfizer MSDS [Link]
  45. Doxorubicin Hydrochloride Cayman Chemical MSDS [Link]
  46. FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, powder, lyophilized, for solution [Link]
  47. FDA Approved Drug Products: DOXORUBICIN HYDROCHLORIDE injection, suspension, liposomal [Link]
Human Metabolome Database
HMDB0015132
KEGG Drug
D03899
KEGG Compound
C01661
PubChem Compound
31703
PubChem Substance
46507641
ChemSpider
29400
BindingDB
32022
RxNav
3639
ChEBI
28748
ChEMBL
CHEMBL53463
ZINC
ZINC000003918087
Therapeutic Targets Database
DNC000163
PharmGKB
PA449412
PDBe Ligand
DM2
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Doxorubicin
PDB Entries
151d / 1d12 / 1da9 / 1i1e / 1p20 / 2dr6 / 4dx7 / 4zvm / 5mra / 5om7
show 3 more
FDA label
Download (105 KB)
MSDS
Download (74.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentSafety and Efficacy1
4CompletedHealth Services ResearchBreast Cancer1
4CompletedOtherBreast Cancer / Obesity1
4CompletedOtherHepatocellular Carcinoma1
4CompletedPreventionCarcinoma of Urinary Bladder, Superficial1

Pharmacoeconomics

Manufacturers
  • Ortho biotech products lp
  • Pharmacia and upjohn co
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Pharmachemie bv
  • Teva parenteral medicines inc
  • Bristol myers squibb co
Packagers
  • Alza Corp.
  • APP Pharmaceuticals
  • APPD
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Centocor Ortho Biotech Inc.
  • Mead Johnson and Co.
  • Pfizer Inc.
  • Pharmachemie BV
  • Pharmacia Inc.
  • Schering-Plough Inc.
  • Sopherion Therapeutics LLC
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, solutionParenteral50 MG
Injection, powder, lyophilized, for solutionIntravenous2 mg/1mL
Injection, powder, for solutionIntravenous
InjectionIntravenous2 mg/ml
Powder, for solutionIntravenous10 mg / vial
InjectionParenteral10 mg
InjectionParenteral200 mg
InjectionParenteral50 mg
Injection, powder, for solutionParenteral50 mg
Injection, powder, for solution10 MG/5ML
Injection, powder, for solution50 MG
Injection, solutionIntravenous; Parenteral10 MG/5ML
Injection, solutionIntravenous; Parenteral200 MG/100ML
Injection, solutionIntravenous; Parenteral50 MG/25ML
InjectionParenteral2 mg
SolutionIntravenous10.0 mg
InjectionIntravenous
Injection, solutionIntravenous2 MG/ML
SolutionParenteral10 mg
SolutionParenteral200 mg
SolutionParenteral50 mg
Injection, powder, lyophilized, for solution10 mg
Injection, powder, lyophilized, for solution50 mg
SolutionParenteral2 MG/ML
SuspensionIntravenous2 mg / mL
Injectable, liposomal; injection; solutionIntravenous2 mg/ml
InjectionIntravenous2.00 mg/ml
SolutionIntravenous2 mg/ml
Injectable, liposomalIntravenous2 MG/ML
Injection, powder, lyophilized, for solutionParenteral10 mg
Injection, solutionIntravenous; Intravesical2 mg/ml
Injection, powder, lyophilized, for solutionIntravenous10 mg
Injection, powder, lyophilized, for solutionIntravenous50 mg
Injectable, liposomalIntravenous2 mg/1mL
Injection, suspension, liposomalIntravenous2 mg/1mL
Injection, suspension, liposomalIntravitreal2 mg/1mL
Injection, solutionParenteral10 MG
Injection, solutionParenteral150 MG
SolutionIntravenous; Intravesical2 mg/ml
SuspensionIntravenous2.000 mg
Injection, solution, concentrateIntravenous2 mg/ml
PowderParenteral50 MG
InjectionParenteral2 mg/ml
SolutionIntravenous; Intravesical50 mg
SolutionIntravenous10 mg/5ml
SolutionIntravenous50 mg/25ml
Powder, for solutionIntravenous150 mg / vial
Powder, for solutionIntravenous50 mg / vial
Injection, solutionParenteral2 MG/ML
Injection, solutionParenteral200 MG
InjectionIntravenous10 mg/5mL
InjectionIntravenous2 mg/1mL
InjectionIntravenous20 mg/10mL
InjectionIntravenous200 mg/100mL
InjectionIntravenous50 mg/25mL
Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous; Intravesical2 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1
Injection, powder, lyophilized, for solutionIntravenous150 mg/1
Injection, powder, lyophilized, for solutionIntravenous20 mg/1
Injection, powder, lyophilized, for solutionIntravenous50 mg/1
Injection, solutionIntravenous2 mg/1mL
Powder, for solutionIntravenous; Intravesical10 mg / vial
Powder, for solutionIntravenous; Intravesical150 mg / vial
Powder, for solutionIntravenous; Intravesical50 mg / vial
SolutionIntravenous2 mg / mL
SolutionIntravenous; Intravesical2 mg / mL
Injection, powder, lyophilized, for solutionParenteral100 mg
Injection, powder, lyophilized, for solutionIntravenous; Intravesical10 mg
PowderParenteral10 MG
Injection, solution, concentrateIntravenous; Intravesical2 mg/ml
Injection, powder, for solutionIntravesical
PowderIntravesical
SolutionIntravenous10.000 mg
SuspensionIntravenous2.00 mg
Injection, powder, lyophilized, for solutionIntravenous; Intravesical50 mg
Injection, solution, concentrateIntravenous; Parenteral2 MG/ML
Injection, powder, lyophilized, for solutionParenteral50 mg
Injection, solution, concentrateIntravenous
SolutionIntravenous10 mg
SolutionIntravenous50 mg
SolutionIntravenous; Intravesical2 mg
SolutionIntravenous; Intravesical200000 mg
SolutionParenteral2 mg
Injection, powder, lyophilized, for solutionIntravenous8.333 mg
Injection, solution, concentrateParenteral10 mg/5ml
Injection, solution, concentrateParenteral50 mg/25ml
Injection, solution
Injection, solution, concentrateIntra-arterial; Intravenous; Intravesical2.00 mg
SolutionParenteral10.00 mg
Injection, powder, for solutionIntravenous10 mg
Injection, powder, for solutionIntravenous50 mg
SolutionIntravenous2 mg
Injectable, liposomalIntravenous2 mg / mL
PowderIntravenous; Parenteral50 MG
Injection, powder, for solution10 mg/1vial
Injection; injection, powder, lyophilized, for solution10 mg
Injection, powder, for solution50 mg/1vial
Injection; injection, powder, lyophilized, for solution50 mg
InjectionParenteral10 mg/5ml
InjectionParenteral50 mg/25ml
Injection, powder, lyophilized, for solutionIntravenous100 mg/50mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/25mL
Injection
SuspensionIntravenous2 mg
Injection, powder, for solution
Injection, suspension2 mg/1ml
SolutionParenteral2.000 mg
Injection, solution2 mg/1ml
SolutionParenteral50.000 mg
SolutionParenteral10.000 mg
Solution2 mg/1ml
Powder10 mg/1vial
Powder50 mg/1vial
SuspensionIntravenous2 mg/1ml
Prices
Unit descriptionCostUnit
Doxorubicin 50 mg vial132.0USD vial
Doxil 2 mg/ml vial115.78USD ml
Adriamycin 50 mg vial64.8USD vial
Doxorubicin 10 mg vial44.4USD vial
Adriamycin 20 mg vial26.4USD vial
Adriamycin 10 mg vial13.2USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5013556No1991-05-072009-10-20US flag
CA1338702No1998-11-122013-11-12Canada flag
CA1335565No1995-05-162012-05-16Canada flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)229-231 °CPhysProp
water solubility~10 mg/mlL45250
logP1.27HANSCH,C ET AL. (1995)
Caco2 permeability-6.8ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility1.18 mg/mLALOGPS
logP1.41ALOGPS
logP0.54Chemaxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8.01Chemaxon
pKa (Strongest Basic)10.03Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count12Chemaxon
Hydrogen Donor Count6Chemaxon
Polar Surface Area206.07 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity134.59 m3·mol-1Chemaxon
Polarizability54.62 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.8092
Blood Brain Barrier-0.9951
Caco-2 permeable-0.799
P-glycoprotein substrateSubstrate0.7861
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.9053
CYP450 2C9 substrateNon-substrate0.8042
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5888
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9209
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8911
Ames testAMES toxic0.9198
CarcinogenicityNon-carcinogens0.9534
BiodegradationNot ready biodegradable0.9672
Rat acute toxicity2.6644 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9752
hERG inhibition (predictor II)Non-inhibitor0.7195
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9100210000-2b807cbc2c92b3239ce2
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-006t-0109000000-ac65f689e3fa439adddc
MS/MS Spectrum - , positiveLC-MS/MSsplash10-006t-0109000000-ac65f689e3fa439adddc
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-056v-0205090000-a3af4fb66a78a4f9d0e6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000w-0009130000-ba265262c021bc27de16
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-002e-1508690000-7c8fae113882b86ccf1e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000t-0009110000-26f3bf456970c7bbd515
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-02cu-1530920000-add2a703b4181a58e17c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-029y-1329650000-6eac9f445f5c4ef373d2
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-246.9922172
predicted
DarkChem Lite v0.1.0
[M-H]-233.6495172
predicted
DarkChem Lite v0.1.0
[M-H]-217.38579
predicted
DeepCCS 1.0 (2019)
[M+H]+247.9719172
predicted
DarkChem Lite v0.1.0
[M+H]+234.0055172
predicted
DarkChem Lite v0.1.0
[M+H]+219.21068
predicted
DeepCCS 1.0 (2019)
[M+Na]+247.1927172
predicted
DarkChem Lite v0.1.0
[M+Na]+234.1975172
predicted
DarkChem Lite v0.1.0
[M+Na]+224.81648
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details
1. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Rody A, Karn T, Gatje R, Ahr A, Solbach C, Kourtis K, Munnes M, Loibl S, Kissler S, Ruckhaberle E, Holtrich U, von Minckwitz G, Kaufmann M: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007 Feb;16(1):86-93. Epub 2006 Sep 28. [Article]
  3. Koehn H, Magan N, Isaacs RJ, Stowell KM: Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. Anticancer Drugs. 2007 Apr;18(4):419-25. [Article]
  4. Hayashi S, Hatashita M, Matsumoto H, Shioura H, Kitai R, Kano E: Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction. Int J Mol Med. 2006 Nov;18(5):909-15. [Article]
  5. Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [Article]
  6. Menendez JA, Vellon L, Lupu R: DNA topoisomerase IIalpha (TOP2A) inhibitors up-regulate fatty acid synthase gene expression in SK-Br3 breast cancer cells: in vitro evidence for a 'functional amplicon' involving FAS, Her-2/neu and TOP2A genes. Int J Mol Med. 2006 Dec;18(6):1081-7. [Article]
  7. Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA: Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol Pharmacol. 1994 Apr;45(4):649-56. [Article]
  2. Momparler RL, Karon M, Siegel SE, Avila F: Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976 Aug;36(8):2891-5. [Article]
  3. Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH: Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry. 1990 Mar 13;29(10):2538-49. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Related to nucleologenesis, may play a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPas...
Gene Name
NOLC1
Uniprot ID
Q14978
Uniprot Name
Nucleolar and coiled-body phosphoprotein 1
Molecular Weight
73602.49 Da
References
  1. Kim YK, Lee WK, Jin Y, Lee KJ, Jeon H, Yu YG: Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140. J Biochem Mol Biol. 2006 Nov 30;39(6):774-81. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein kinase c binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name
TOP2B
Uniprot ID
Q02880
Uniprot Name
DNA topoisomerase 2-beta
Molecular Weight
183265.825 Da
References
  1. Khalil OM, Gedawy EM, El-Malah AA, Adly ME: Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg Chem. 2019 Mar;83:262-276. doi: 10.1016/j.bioorg.2018.10.058. Epub 2018 Oct 30. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
L-glucuronate reductase activity
Specific Function
Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyd...
Gene Name
AKR1A1
Uniprot ID
P14550
Uniprot Name
Alcohol dehydrogenase [NADP(+)]
Molecular Weight
36572.71 Da
References
  1. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glyceraldehyde oxidoreductase activity
Specific Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name
AKR1B1
Uniprot ID
P15121
Uniprot Name
Aldose reductase
Molecular Weight
35853.125 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Novotna R, Wsol V, Xiong G, Maser E: Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. doi: 10.1016/j.toxlet.2008.06.858. Epub 2008 Jun 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinal dehydrogenase activity
Specific Function
Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid...
Gene Name
AKR1C4
Uniprot ID
P17516
Uniprot Name
Aldo-keto reductase family 1 member C4
Molecular Weight
37066.52 Da
References
  1. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinal dehydrogenase activity
Specific Function
Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldeh...
Gene Name
AKR1B10
Uniprot ID
O60218
Uniprot Name
Aldo-keto reductase family 1 member B10
Molecular Weight
36019.295 Da
References
  1. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Prostaglandin-e2 9-reductase activity
Specific Function
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. ...
Gene Name
CBR1
Uniprot ID
P16152
Uniprot Name
Carbonyl reductase [NADPH] 1
Molecular Weight
30374.73 Da
References
  1. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nadph binding
Specific Function
Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro).
Gene Name
CBR3
Uniprot ID
O75828
Uniprot Name
Carbonyl reductase [NADPH] 3
Molecular Weight
30849.97 Da
References
  1. Bains OS, Karkling MJ, Lubieniecka JM, Grigliatti TA, Reid RE, Riggs KW: Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63. doi: 10.1124/jpet.109.160614. Epub 2009 Dec 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Inducer
Curator comments
There are limited data in the literature supporting the inhibitory actions of this drug on CYP1B1. The majority of the data suggests that it is an inducer of CYP1B1.
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Zordoky BN, El-Kadi AO: Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells. Vascul Pharmacol. 2008 Oct-Dec;49(4-6):166-72. doi: 10.1016/j.vph.2008.07.004. Epub 2008 Jul 25. [Article]
  2. Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [Article]
  3. Zordoky BN, Anwar-Mohamed A, Aboutabl ME, El-Kadi AO: Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver. Drug Metab Dispos. 2011 Aug;39(8):1440-50. doi: 10.1124/dmd.111.039123. Epub 2011 May 13. [Article]
  4. Grant MK, Seelig DM, Sharkey LC, Zordoky BN: Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice. Biol Sex Differ. 2017 Jan 7;8:1. doi: 10.1186/s13293-016-0124-4. eCollection 2017. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Masek V, Anzenbacherova E, Etrych T, Strohalm J, Ulbrich K, Anzenbacher P: Interaction of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates with human liver microsomal cytochromes P450: comparison with free doxorubicin. Drug Metab Dispos. 2011 Sep;39(9):1704-10. doi: 10.1124/dmd.110.037986. Epub 2011 Jun 3. [Article]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
  3. Potential CYP2B6 Substrates, Inhibitors, Inudcers (https://ctep.cancer.gov/protocoldevelopment/docs/cyp2b6.doc) [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [Article]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lu H, Chen CS, Waxman DJ: Potentiation of methoxymorpholinyl doxorubicin antitumor activity by P450 3A4 gene transfer. Cancer Gene Ther. 2009 May;16(5):393-404. doi: 10.1038/cgt.2008.93. Epub 2008 Nov 14. [Article]
  2. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R: Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61. [Article]
  3. Diaz Flaque MC, Cayrol MF, Sterle HA, Del Rosario Aschero M, Diaz Albuja JA, Isse B, Farias RN, Cerchietti L, Rosemblit C, Cremaschi GA: Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells. Oncotarget. 2019 Apr 30;10(32):3051-3065. doi: 10.18632/oncotarget.26890. eCollection 2019 Apr 30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
References
  1. Gutierrez PL, Gee MV, Bachur NR: Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Superoxide dismutase activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vit...
Gene Name
NQO1
Uniprot ID
P15559
Uniprot Name
NAD(P)H dehydrogenase [quinone] 1
Molecular Weight
30867.405 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  2. Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Ubiquitin protein ligase binding
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS2
Uniprot ID
O75306
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
Molecular Weight
52545.26 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nadh dehydrogenase activity
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS3
Uniprot ID
O75489
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
Molecular Weight
30241.245 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Quinone binding
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS7
Uniprot ID
O75251
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
Molecular Weight
23563.3 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [Article]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. P...
Gene Name
NOS1
Uniprot ID
P29475
Uniprot Name
Nitric oxide synthase, brain
Molecular Weight
160969.095 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induce...
Gene Name
NOS3
Uniprot ID
P29474
Uniprot Name
Nitric oxide synthase, endothelial
Molecular Weight
133287.62 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity ...
Gene Name
NOS2
Uniprot ID
P35228
Uniprot Name
Nitric oxide synthase, inducible
Molecular Weight
131116.3 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [Article]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [Article]
  2. Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Kratz F, Mansour A, Soltau J, Warnecke A, Fichtner I, Unger C, Drevs J: Development of albumin-binding doxorubicin prodrugs that are cleaved by prostate-specific antigen. Arch Pharm (Weinheim). 2005 Oct;338(10):462-72. [Article]
  2. Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F: Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007 May-Jun;18(3):702-16. Epub 2007 Mar 23. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Fardel O, Lecureur V, Daval S, Corlu A, Guillouzo A: Up-regulation of P-glycoprotein expression in rat liver cells by acute doxorubicin treatment. Eur J Biochem. 1997 May 15;246(1):186-92. [Article]
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [Article]
  3. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [Article]
  4. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [Article]
  5. Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. [Article]
  6. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
  7. Kim S, Kim SS, Bang YJ, Kim SJ, Lee BJ: In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines. Peptides. 2003 Jul;24(7):945-53. [Article]
  8. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I: Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6. [Article]
  9. Kusunoki N, Takara K, Tanigawara Y, Yamauchi A, Ueda K, Komada F, Ku Y, Kuroda Y, Saitoh Y, Okumura K: Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein. Jpn J Cancer Res. 1998 Nov;89(11):1220-8. [Article]
  10. Li YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK: Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Chemotherapy. 2004 Jun;50(2):55-62. [Article]
  11. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. doi: 10.1002/ijc.24885. [Article]
  12. Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [Article]
  13. Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [Article]
  14. Woodahl EL, Crouthamel MH, Bui T, Shen DD, Ho RJ: MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. doi: 10.1007/s00280-008-0906-4. Epub 2009 Jan 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [Article]
  2. Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. [Article]
  3. Tribull TE, Bruner RH, Bain LJ: The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett. 2003 Apr 30;142(1-2):61-70. [Article]
  4. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. [Article]
  5. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [Article]
  6. Wong IL, Chan KF, Tsang KH, Lam CY, Zhao Y, Chan TH, Chow LM: Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives. J Med Chem. 2009 Sep 10;52(17):5311-22. doi: 10.1021/jm900194w. [Article]
  7. Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [Article]
  8. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name
ABCC6
Uniprot ID
O95255
Uniprot Name
Multidrug resistance-associated protein 6
Molecular Weight
164904.81 Da
References
  1. Cai J, Daoud R, Alqawi O, Georges E, Pelletier J, Gros P: Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6). Biochemistry. 2002 Jun 25;41(25):8058-67. [Article]
  2. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [Article]
  2. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [Article]
  3. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [Article]
  4. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [Article]
  5. An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [Article]
  6. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [Article]
  7. Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [Article]
  8. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic cation transmembrane transporter activity
Specific Function
High affinity carnitine transporter; the uptake is partially sodium-ion dependent. Thought to mediate the L-carnitine secretion mechanism from testis epididymal epithelium into the lumen which is i...
Gene Name
SLC22A16
Uniprot ID
Q86VW1
Uniprot Name
Solute carrier family 22 member 16
Molecular Weight
64613.58 Da
References
  1. Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Not Available
Gene Name
ABCB8
Uniprot ID
Q9NUT2
Uniprot Name
ATP-binding cassette sub-family B member 8, mitochondrial
Molecular Weight
79988.17 Da
References
  1. Elliott AM, Al-Hajj MA: ABCB8 mediates doxorubicin resistance in melanoma cells by protecting the mitochondrial genome. Mol Cancer Res. 2009 Jan;7(1):79-87. doi: 10.1158/1541-7786.MCR-08-0235. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane transporter activity
Specific Function
Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the ma...
Gene Name
RALBP1
Uniprot ID
Q15311
Uniprot Name
RalA-binding protein 1
Molecular Weight
76062.86 Da
References
  1. Singhal SS, Singhal J, Nair MP, Lacko AG, Awasthi YC, Awasthi S: Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Folmer Y, Schneider M, Blum HE, Hafkemeyer P: Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. Cancer Gene Ther. 2007 Nov;14(11):875-84. Epub 2007 Aug 17. [Article]

Drug created at June 13, 2005 13:24 / Updated at June 14, 2024 16:06