Melphalan

Identification

Summary

Melphalan is an alkylating agent used to treat multiple myeloma, ovarian carcinoma, uveal melanoma with unresectable hepatic metastases, and for high-dose conditioning before hematopoietic stem cell transplant in patients.

Brand Names
Alkeran, Evomela, Hepzato
Generic Name
Melphalan
DrugBank Accession Number
DB01042
Background

Melphalan is a nitrogen mustard or bischloroethylamine type alkylating agent.7 It was first synthesized in the early 1950s by substituting L-phenylalanine for the methyl group on nitrogen mustard.4,5 Melphalan is used in the treatment of multiple myeloma and ovarian carcinoma.7 It is also used for high-conditioning before hematopoietic stem cell transplant.8 It is also used to treat uveal melanoma with unresectable hepatic metastases.9

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 305.2
Monoisotopic: 304.074533244
Chemical Formula
C13H18Cl2N2O2
Synonyms
  • 3-(p-(Bis(2-chloroethyl)amino)phenyl)-L-alanine
  • 3-p-(Di(2-chloroethyl)amino)-phenyl-L-alanine
  • 4-(Bis(2-chloroethyl)amino)-L-phenylalanine
  • L-3-(p-(Bis(2-chloroethyl)amino)phenyl)alanine
  • L-PAM
  • L-Phenylalanine mustard
  • L-Sarcolysine
  • Melfalano
  • Melphalan
  • Melphalanum
  • p-Bis(beta-chloroethyl)aminophenylalanine
  • p-Di-(2-chloroethyl)amino-L-phenylalanine
  • p-L-Sarcolysin
  • p-N-Bis(2-chloroethyl)amino-L-phenylalanine
  • p-N,N-bis(2-chloroethyl)amino-L-phenylalanine
  • Phenylalanine mustard
  • Phenylalanine nitrogen mustard
External IDs
  • CB 3025
  • CB-3025
  • NCI-C04853
  • NSC-241286
  • NSC-8806
  • SK 15673
  • SK-15673

Pharmacology

Indication

Melphalan is indicated for use as a high-dose conditioning treatment prior to hematopoietic stem cell transplantation in patients with multiple myeloma.8 It is also indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.7

Melphalan is a component of HEPZATO KIT, a liver-directed therapy indicated for the treatment of adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMultiple myeloma (mm)••••••••••••••••••
Treatment ofUnresectable hepatic metastases••••••••••••••••••••••••• •• ••••••••• •• •••••••••• ••••• ••••••••
Treatment ofUnresectable ovarian cancer (epithelial)••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Melphalan possesses cytotoxic, immunosuppressive, and myeloablative activities.4,7 Melphalan produces chromosomal aberrations in vitro and in vivo; thus, it is considered to be potentially leukemogenic in humans. It also causes dose-limiting bone marrow suppression. The peak mean heart rate increased by 20 bpm from baseline following melphalan 100 mg/m2 for two consecutive days in multiple myeloma patients undergoing autologous stem cell transplantation.8

Mechanism of action

Melphalan is an alkylating agent of the bischloroethylamine type.8 It is believed to be taken up by tumour cells via a neutral amino acid active pathway shared by leucine.5 Melphalan binds at the N7 position of guanine and induces inter-strand cross-links in DNA, disrupting DNA synthesis or transcription. It can also cause DNA-protein cross-linking and induce lesions in RNA, proteins, and lipids.1,2,3,5,6,8 Melphalan is cytotoxic in resting and rapidly dividing tumour cells.8

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
Absorption

The absorption of oral melphalan is highly variable concerning both the time to the first appearance of the drug in plasma (range: 0 to 6 hours) and peak plasma concentration (Cmax). The average absolute bioavailability of melphalan ranges from 56% to 93%. High variability in bioavailability may be due to incomplete intestinal absorption, variable first-pass hepatic metabolism, or rapid hydrolysis. Tmax was one hour in patients who received single oral doses of 0.2 mg/kg to 0.25 mg/kg of melphalan. Oral administration of melphalan with a high-fat meal may reduce melphalan exposure (AUC) by 36% to 54%.7

Mean (± SD) Cmax and AUC0-inf were 5.8 ± 1.5 mcg/mL and 451 ± 109 mcg x min/mL, respectively, following intravenous administration of 100 mg/m2 in multiple myeloma patients.8

Volume of distribution

The volume of distribution of melphalan ranges from approximately 35.5 to 185.7 L/m2.8 Penetration into cerebrospinal fluid is low.7

Protein binding

Protein binding of melphalan ranges from 50% to 90%. Serum albumin is the major binding protein, accounting for approximately 40% to 60% of the plasma protein binding, while α1-acid glycoprotein accounts for about 20% of the plasma protein binding. Approximately 30% of melphalan is covalently and irreversibly bound to plasma proteins.7,8

Metabolism

Melphalan primarily undergoes chemical hydrolysis to inactive metabolites, monohydroxymelphalan and dihydroxymelphalan.7,8 No other melphalan metabolites have been observed in humans.7

Hover over products below to view reaction partners

Route of elimination

About 5.8% to 21.3% of melphalan is excreted in urine.8

Half-life

In patients given a single oral dose of 0.6 mg/kg of melphalan, the terminal elimination plasma half-life (± SD) was 1.5 ± 0.83 hours.7 Following intravenous administration, the terminal elimination half-life is approximately 75 minutes.8

Clearance

Average total body clearance (CL) ranges from approximately 250 to 325 mL/min/m2.8

Adverse Effects
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Toxicity

The oral and intraperitoneal LD50 in rats is 4484 µg/kg and 11200 µg/kg, respectively. The subcutaneous LD50 in mice is 32 mg/kg.10

Overdoses resulting in death have been reported with melphalan. Overdoses, including intravenous doses up to 290 mg/m2 and oral doses up to 50 mg/day for 16 days, have been reported. Symptoms of overdose include severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, cholinomimetic effects, mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract. Elevations in liver enzymes and veno-occlusive disease occur infrequently. Significant hyponatremia, caused by an associated inappropriate secretion of ADH syndrome, has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely. The principal toxic effect is bone marrow suppression. Melphalan is not removed from plasma via hemodialysis, and overdose is typically managed by general supportive measures, with appropriate blood transfusions and antibiotics.7,8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

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
AbataceptThe risk or severity of adverse effects can be increased when Melphalan is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Melphalan.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Melphalan.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Melphalan.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Melphalan.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Melphalan hydrochloride1VXP4V453T3223-07-2OUUYBRCCFUEMLH-YDALLXLXSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlkeranTablet2 mgOralAspen Pharmacare Canada Inc.1964-12-31Not applicableCanada flag
AlkeranInjection, powder, for solution; Kit50 mg/10mLIntravenousApoPharma USA, Inc.2011-01-01Not applicableUS flag
AlkeranTablet, film coated2 mg/1OralPhysicians Total Care, Inc.2005-08-152012-06-30US flag
AlkeranKit50 mg/10mLIntravenousCelgene1993-03-162009-11-02US flag
AlkeranTablet, film coated2 mg/1OralGlaxosmithkline Inc1984-05-102012-04-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Melphalan50 mg/50mgIntravenousBpi Labs Llc2020-09-30Not applicableUS flag
MelphalanTablet2 mg/1OralAlvogen Inc.2017-03-222024-05-01US flag
MelphalanInjection, powder, for solution; Kit50 mg/10mLIntravenousFresenius Kabi USA, LLC2017-12-22Not applicableUS flag
Melphalan HydrochlorideKit50 mg/10mLIntravenousActavis Pharma, Inc.2017-01-13Not applicableUS flag
Melphalan HydrochlorideKit50 mg/10mLIntravenousSagent Pharmaceuticals2017-03-152020-04-30US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AlkeranMelphalan (50 mg)Kit; Powder, for solution; SolutionIntra-arterial; IntravenousAspen Pharmacare Canada Inc.1995-12-31Not applicableCanada flag
Hepzato KitMelphalan hydrochloride (50 mg/10mL) + Sodium chloride (0.9 mg/100mL)KitIntra-arterialDelcath Systems, Inc.2023-12-04Not applicableUS flag
Melphalan for InjectionMelphalan (50 mg)Kit; Powder, for solution; SolutionIntra-arterial; IntravenousMarcan Pharmaceuticals Inc2018-06-18Not applicableCanada flag
Melphalan for InjectionMelphalan (50 mg)Kit; Powder, for solution; SolutionIntravenousApotex Corporation2018-11-20Not applicableCanada flag
Taro-melphalanMelphalan (50 mg)Kit; Powder, for solutionIntra-arterial; IntravenousTaro Pharmaceuticals, Inc.2021-01-25Not applicableCanada flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ALKERAN 2 MG TABLET, 25 ADETMelphalan (2 mg)TabletOralVLD DANIŞMANLIK TIBBİ ÜRÜNLER VE TANITIM HİZMETLERİ LTD. ŞTİ.2018-05-22Not applicableTurkey flag

Categories

ATC Codes
L01AA03 — Melphalan
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Phenylpropanoic acids / Amphetamines and derivatives / L-alpha-amino acids / Aniline and substituted anilines / Dialkylarylamines / Nitrogen mustard compounds / Aralkylamines / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids
show 7 more
Substituents
3-phenylpropanoic-acid / Alkyl chloride / Alkyl halide / Alpha-amino acid / Amine / Amino acid / Amphetamine or derivatives / Aniline or substituted anilines / Aralkylamine / Aromatic homomonocyclic compound
show 22 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organochlorine compound, non-proteinogenic L-alpha-amino acid, L-phenylalanine derivative, nitrogen mustard (CHEBI:28876)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Q41OR9510P
CAS number
148-82-3
InChI Key
SGDBTWWWUNNDEQ-LBPRGKRZSA-N
InChI
InChI=1S/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1
IUPAC Name
(2S)-2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid
SMILES
N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O

References

Synthesis Reference
US3032584
General References
  1. Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. doi: 10.1021/tx7004508. Epub 2008 Feb 14. [Article]
  2. Povirk LF, Shuker DE: DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res. 1994 Dec;318(3):205-26. doi: 10.1016/0165-1110(94)90015-9. [Article]
  3. Lawley PD, Phillips DH: DNA adducts from chemotherapeutic agents. Mutat Res. 1996 Aug 17;355(1-2):13-40. doi: 10.1016/0027-5107(96)00020-6. [Article]
  4. Bayraktar UD, Bashir Q, Qazilbash M, Champlin RE, Ciurea SO: Fifty years of melphalan use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013 Mar;19(3):344-56. doi: 10.1016/j.bbmt.2012.08.011. Epub 2012 Aug 24. [Article]
  5. Kuczma M, Ding ZC, Zhou G: Immunostimulatory Effects of Melphalan and Usefulness in Adoptive Cell Therapy with Antitumor CD4+ T Cells. Crit Rev Immunol. 2016;36(2):179-191. doi: 10.1615/CritRevImmunol.2016017507. [Article]
  6. Poczta A, Rogalska A, Marczak A: Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies-Current Research and Clinical Approaches. J Clin Med. 2021 Apr 23;10(9):1841. doi: 10.3390/jcm10091841. [Article]
  7. DailyMed: Melphalan USP tablets for oral use [Link]
  8. FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]
  9. FDA Approved Drug Products: HEPZATO (melphalan) KIT Hepatic Delivery System (HDS) for intra-arterial use [Link]
  10. Cayman Chemical: Melphalan MSDS [Link]
Human Metabolome Database
HMDB0015176
KEGG Drug
D00369
KEGG Compound
C07122
PubChem Compound
460612
PubChem Substance
46509130
ChemSpider
405297
BindingDB
50025837
RxNav
6718
ChEBI
28876
ChEMBL
CHEMBL852
ZINC
ZINC000000001673
Therapeutic Targets Database
DAP000791
PharmGKB
PA450354
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Melphalan

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Antibioticos Ltd.
  • Bioniche Pharma
  • Cardinal Health
  • Catalent Pharma Solutions
  • Generamedix Inc.
  • GlaxoSmithKline Inc.
  • Nerviano Medical Science S.R.L.
  • Oso Biopharmaceuticals Manufacturing LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionParenteral50 MG/10ML
Injection, powder, for solution; kitIntravenous50 mg/10mL
Kit; powder, for solution; solutionIntra-arterial; Intravenous
TabletOral2 mg
TabletOral2 mg/1
TabletOral5 MG
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral2 MG
Tablet; tablet, film coatedOral2 MG
Tablet, film coatedOral
InjectionIntravenous50 mg
Injection, powder, lyophilized, for solutionIntravenous
Tablet, film coatedOral2.00 mg
TabletOral
Tablet, film coatedOral200000 mg
Injection, powder, lyophilized, for solutionParenteral50 mg
Injection, powder, lyophilized, for solutionParenteral5000000 mg
Injection, powder, lyophilized, for solutionIntravenous50 mg/10mL
KitIntra-arterial
Injection, powder, for solution50 MG
Injection, powder, for solutionIntravenous
Injection, powder, for solutionParenteral50 mg
Kit; powder, for solutionIntravenous50 mg / vial
Kit; powder, for solution; solutionIntravenous
KitIntravenous50 mg/10mL
KitIntravenous50 mg/15mL
SolutionParenteral50 mg
Injection, powder, for solutionParenteral
Injection, powder, lyophilized, for solutionIntravenous50 mg
Injection, powder, for solutionIntravenous200 mg
Injection, powder, for solutionIntravenous50 mg
PowderIntravenous200 MG
PowderIntravenous50 MG
Kit; powder, for solutionIntra-arterial; Intravenous
PowderIntravenous50 mg/1vial
Tablet, coatedOral2 mg
Prices
Unit descriptionCostUnit
Alkeran 50 mg vial1971.72USD vial
Melphalan hcl 50 mg vial1845.6USD vial
Alkeran 2 mg tablet5.65USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA1341114No2000-10-102017-10-10Canada flag
US8410077No2013-04-022029-03-13US flag
US9200088No2015-12-012029-03-13US flag
US9493582No2016-11-152033-02-27US flag
US10040872No2018-08-072034-01-30US flag
US10864183No2020-12-152030-05-28US flag
US10940128No2021-03-092030-06-14US flag
US11020363No2021-06-012030-05-28US flag
US11633528No2012-11-072032-11-07US flag
US10369264No2019-08-062032-11-07US flag
US10098997No2018-10-162032-11-07US flag
US11083831No2021-08-102032-12-30US flag
US10537520No2020-01-212036-06-29US flag
US10195334No2019-02-052033-01-16US flag
US11241522No2012-11-072032-11-07US flag
US9314561No2016-04-192034-02-07US flag
US9707331No2017-07-182034-09-17US flag
US10569004No2020-02-252032-11-07US flag
US11833286No2012-12-302032-12-30US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180https://www.fishersci.com/store/msds?partNumber=AC458650010&productDescription=MELPHALAN%2C+94%25+1GR&vendorId=VN00032119&countryCode=US&language=en
Predicted Properties
PropertyValueSource
logP0.25Chemaxon
pKa (Strongest Acidic)1.29Chemaxon
pKa (Strongest Basic)9.51Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area66.56 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity78.23 m3·mol-1Chemaxon
Polarizability31.38 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9523
Blood Brain Barrier-0.6073
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.983
P-glycoprotein inhibitor IINon-inhibitor0.9192
Renal organic cation transporterNon-inhibitor0.811
CYP450 2C9 substrateNon-substrate0.8457
CYP450 2D6 substrateNon-substrate0.7432
CYP450 3A4 substrateNon-substrate0.7553
CYP450 1A2 substrateInhibitor0.779
CYP450 2C9 inhibitorNon-inhibitor0.9348
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9193
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9863
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.7873
BiodegradationNot ready biodegradable0.9746
Rat acute toxicity3.9179 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8187
hERG inhibition (predictor II)Non-inhibitor0.8488
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-MSsplash10-052f-3890000000-153ff87813e7a797c73b
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000w-2930000000-b95beb5e9c3e61b7687f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000w-2930000000-b95beb5e9c3e61b7687f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-0093000000-763069c4ed3fab513a15
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9023000000-602fbbccaeedbb0341a7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-0e0586f1de75c5d62459
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00bi-0190000000-e71f2a817d811f2f16d6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9240000000-d0bc6a6319a85f9112e8
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014l-0930000000-883b8aba03bfd9f46721
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-172.3496644
predicted
DarkChem Lite v0.1.0
[M-H]-166.4261
predicted
DeepCCS 1.0 (2019)
[M+H]+172.9870644
predicted
DarkChem Lite v0.1.0
[M+H]+168.7841
predicted
DeepCCS 1.0 (2019)
[M+Na]+172.5926644
predicted
DarkChem Lite v0.1.0
[M+Na]+174.87724
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.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Cross-linking/alkylation
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Monahan SD, Subbotin VM, Budker VG, Slattum PM, Neal ZC, Herweijer H, Wolff JA: Rapidly reversible hydrophobization: an approach to high first-pass drug extraction. Chem Biol. 2007 Sep;14(9):1065-77. [Article]
  4. Lee PC, Kakadiya R, Su TL, Lee TC: Combination of bifunctional alkylating agent and arsenic trioxide synergistically suppresses the growth of drug-resistant tumor cells. Neoplasia. 2010 May;12(5):376-87. [Article]
  5. Wang F, Li F, Ganguly M, Marky LA, Gold B, Egli M, Stone MP: A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry. 2008 Jul 8;47(27):7147-57. doi: 10.1021/bi800375m. Epub 2008 Jun 13. [Article]
  6. Vasquez KM: Targeting and processing of site-specific DNA interstrand crosslinks. Environ Mol Mutagen. 2010 Jul;51(6):527-39. doi: 10.1002/em.20557. [Article]
  7. Dimopoulos MA, Souliotis VL, Anagnostopoulos A, Bamia C, Pouli A, Baltadakis I, Terpos E, Kyrtopoulos SA, Sfikakis PP: Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma. Haematologica. 2007 Nov;92(11):1505-12. [Article]
  8. Chen Q, Van der Sluis PC, Boulware D, Hazlehurst LA, Dalton WS: The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells. Blood. 2005 Jul 15;106(2):698-705. Epub 2005 Mar 31. [Article]
  9. Souliotis VL, Dimopoulos MA, Episkopou HG, Kyrtopoulos SA, Sfikakis PP: Preferential in vivo DNA repair of melphalan-induced damage in human genes is greatly affected by the local chromatin structure. DNA Repair (Amst). 2006 Aug 13;5(8):972-85. Epub 2006 Jun 15. [Article]
  10. Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N: Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr;21(4):787-95. doi: 10.1021/tx7004508. Epub 2008 Feb 14. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
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. FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. FDA Approved Drug Products: EVOMELA (melphalan) for injection, for intravenous use (April 2022) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. doi: 10.1158/0008-5472.CAN-08-2483. Epub 2009 Feb 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Peptide antigen binding
Specific Function
Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular a...
Gene Name
SLC7A5
Uniprot ID
Q01650
Uniprot Name
Large neutral amino acids transporter small subunit 1
Molecular Weight
55009.62 Da
References
  1. Moscow JA, Swanson CA, Cowan KH: Decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan. Br J Cancer. 1993 Oct;68(4):732-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Neutral amino acid transmembrane transporter activity
Specific Function
Sodium-independent, high affinity transport of small neutral D- and L-amino acids. May play a role in the modulation of glutamatergic transmission through mobilization of D-serine at the glutamater...
Gene Name
SLC7A10
Uniprot ID
Q9NS82
Uniprot Name
Asc-type amino acid transporter 1
Molecular Weight
56797.4 Da
References
  1. Moscow JA, Swanson CA, Cowan KH: Decreased melphalan accumulation in a human breast cancer cell line selected for resistance to melphalan. Br J Cancer. 1993 Oct;68(4):732-7. [Article]

Drug created at June 13, 2005 13:24 / Updated at April 13, 2024 19:42