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Identification
- Summary
Cabazitaxel is an antineoplastic agent used in combination with corticosteroids to treat metastatic castration-resistant prostate cancer in patients previously treated with a docetaxel-containing treatment regimen.
- Brand Names
- Jevtana
- Generic Name
- Cabazitaxel
- DrugBank Accession Number
- DB06772
- Background
Cabazitaxel is a taxoid synthesized from 10-deacetylbaccatin III, a compound isolated from the yew tree.4 As a second-generation semisynthetic microtubule inhibitor, cabazitaxel stabilizes microtubules and induces tumour cell death.2 Due to its low affinity for the P-glycoprotein (P-gp) efflux pump, cabazitaxel can more readily penetrate the blood–brain barrier compared to other taxanes like paclitaxel and docetaxel.2,3,4
Cabazitaxel is used to treat metastatic castration-resistant prostate cancer. It was first approved by the FDA on June 17, 2010.3 It was also approved by the EMA on March 17, 2011 7 and Health Canada on December 17, 2019.6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Cabazitaxel (DB06772)
- Weight
- Average: 835.9324
Monoisotopic: 835.377905537 - Chemical Formula
- C45H57NO14
- Synonyms
- 1-HYDROXY-7.BETA.,10.BETA.-DIMETHOXY-9-OXO-5.BETA.,20-EPOXYTAX-11-ENE-2.ALPHA.,4,13.ALPHA.-TRIYL 4-ACETATE 2-BENZOATE 13-((2R,3S)-3-(((TERT-BUTOXY)CARBONYL)AMINO)-2-HYDROXY-3-PHENYLPROPANOATE)
- Cabazitaxel
- Cabazitaxelum
- External IDs
- RPR-116258A
- RPR116258
- RPR116258A
- TXD 258
- TXD-258
- TXD258
- XRP 6258
- XRP-6258
- XRP6258
Pharmacology
- Indication
Cabazitaxel is indicated, in combination with prednisone, for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen.5 In Europe and Canada, it can also be used in combination with prednisolone.6,7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Metastatic castration-resistant prostate cancer (mcrpc) Regimen in combination with: Prednisolone (DB00860) •••••••••••• •••••••• ••••••••• ••••••••• Used in combination to treat Metastatic castration-resistant prostate cancer (mcrpc) Regimen in combination with: Prednisone (DB00635) •••••••••••• •••••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Cabazitaxel demonstrates a broad spectrum of antitumour activity against advanced human tumours xenografted in mice, including intracranial human glioblastomas.6 Cabazitaxel has a low affinity to P-glycoprotein, allowing it to penetrate the blood-brain barrier without being subject to extensive P-gp-mediated active efflux.3,4 Cabazitaxel works against docetaxel-sensitive tumours and tumour models resistant to docetaxel and other chemotherapy drugs.4,6
- Mechanism of action
Microtubules are cytoskeletal polymers that regulate cell shape, vesicle transport, cell signalling, and cell division. They are made up of alpha-tubulin and beta-tubulin heterodimers. Microtubules extend toward the mitotic spindle during mitosis to allow the separation and distribution of chromosomes during cell division.2 Cabazitaxel binds to the N-terminal amino acids of the beta-tubulin subunit and promotes microtubule polymerization while simultaneously inhibiting disassembly: this results in the stabilization of microtubules, preventing microtubule cell division. Cabazitaxel ultimately blocks mitotic and interphase cellular functions and tumour proliferation.2,5
Target Actions Organism ATubulin beta-1 chain inhibitorHumans - Absorption
Based on the population pharmacokinetic analysis, after an intravenous dose of cabazitaxel 25 mg/m2 every three weeks, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng x h/mL (CV 34%). No major deviation from the dose proportionality was observed from 10 to 30 mg/m2 in patients with advanced solid tumours.5
- Volume of distribution
Steady-state volume of distribution (Vss) was 4,864 L (2,643 L/m2 for a patient with a median BSA of 1.84 m2).5
- Protein binding
In vitro, the binding of cabazitaxel to human serum proteins was 89% to 92% and was not saturable up to 50,000 ng/mL. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). The in vitro blood-to-plasma concentration ratio in human blood ranged from 0.90 to 0.99, indicating that cabazitaxel was equally distributed between blood and plasma.5
- Metabolism
More than 95% of cabazitaxel is extensively metabolized in the liver. CYP3A4 and CYP3A5 are responsible for 80% to 90% of drug metabolism, while CYP2C8 is involved to a lesser extent. While cabazitaxel is the main circulating moiety in human plasma, seven metabolites have been detected in plasma, including three active metabolites arising from O-demethylation 5 - docetaxel, RPR112698, and RPR123142.1 The main metabolite accounts for 5% of total cabazitaxel exposure.5
Hover over products below to view reaction partners
- Route of elimination
After a one-hour intravenous infusion [14C]-cabazitaxel 25 mg/m2, approximately 80% of the administered dose was eliminated within two weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose), while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine). Around 20 metabolites of cabazitaxel are excreted into human urine and feces.5
- Half-life
Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of four minutes, two hours, and 95 hours, respectively.5
- Clearance
Based on the population pharmacokinetic analysis, cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m2 for a patient with a median BSA of 1.84 m2) in patients with metastatic prostate cancer.5
- Adverse Effects
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The oral LD50 in rats is 500 mg/kg.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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Cabazitaxel can be increased when it is combined with Abametapir. Abatacept The metabolism of Cabazitaxel can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Cabazitaxel. Abiraterone The metabolism of Cabazitaxel can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Cabazitaxel can be decreased when combined with Acalabrutinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of cabazitaxel, which may increase its serum concentration.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of cabazitaxel and may reduce its serum concentration.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cabazitaxel Accord Injection, solution, concentrate 20 mg/ml Intravenous Accord Healthcare, S.L.U. 2020-12-23 Not applicable EU 
Cabazitaxel for Injection Solution 40 mg / mL Intravenous Dr. Reddy's Laboratories Limited 2020-06-01 Not applicable Canada 
Cabazitaxel for Injection Solution 45 mg / 4.5 mL Intravenous Sandoz S.P.A. 2019-12-18 Not applicable Canada Cabazitaxel for Injection Solution 60 mg / 6 mL Intravenous Sandoz S.P.A. 2019-12-18 Not applicable Canada Cabazitaxel for Injection Kit; Solution 40 mg / mL Intravenous Marcan Pharmaceuticals Inc Not applicable Not applicable Canada
Categories
- ATC Codes
- L01CD04 — Cabazitaxel
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Cardiotoxic antineoplastic agents
- Cyclodecanes
- Cycloparaffins
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Diterpenes
- Immunosuppressive Agents
- Microtubule Inhibition
- Microtubule Inhibitors
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Taxane Derivatives
- Taxoids
- Terpenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as taxanes and derivatives. These are diterpenoids with a structure based either on the taxane skeleton, or a derivative thereof. In term of phytochemistry, several derivatives of the taxane skeleton exist: 2(3->20)-abeotaxane, 3,11-cyclotaxane, 11(15->1),11(10->9)-abeotaxane, 3,8-seco-taxane, and 11(15->1)-abeotaxane, among others. More complex skeletons have been found recently, which include the taxane-derived [3.3.3] propellane ring system.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Prenol lipids
- Sub Class
- Diterpenoids
- Direct Parent
- Taxanes and derivatives
- Alternative Parents
- Benzoic acid esters / Tricarboxylic acids and derivatives / Benzoyl derivatives / Fatty acid esters / Monosaccharides / Tertiary alcohols / Carbamate esters / Secondary alcohols / Oxetanes / Carboxylic acid esters show 8 more
- Substituents
- Alcohol / Aromatic heteropolycyclic compound / Benzenoid / Benzoate ester / Benzoic acid or derivatives / Benzoyl / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tetracyclic diterpenoid (CHEBI:63584)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 51F690397J
- CAS number
- 183133-96-2
- InChI Key
- BMQGVNUXMIRLCK-OAGWZNDDSA-N
- InChI
- InChI=1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1
- IUPAC Name
- (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
- SMILES
- [H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C4=CC=CC=C4)C(C)=C([C@@H](OC)C(=O)[C@]1(C)[C@H](C[C@H]1OC[C@@]21OC(C)=O)OC)C3(C)C
References
- Synthesis Reference
Nagesh Palepu, "CABAZITAXEL FORMULATIONS AND METHODS OF PREPARING THEREOF." U.S. Patent US20120065255, issued March 15, 2012.
US20120065255- General References
- Kort A, Hillebrand MJ, Cirkel GA, Voest EE, Schinkel AH, Rosing H, Schellens JH, Beijnen JH: Quantification of cabazitaxel, its metabolite docetaxel and the determination of the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Apr 15;925:117-23. doi: 10.1016/j.jchromb.2013.02.034. Epub 2013 Mar 5. [Article]
- Nightingale G, Ryu J: Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. P T. 2012 Aug;37(8):440-8. [Article]
- Paller CJ, Antonarakis ES: Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer. Drug Des Devel Ther. 2011 Mar 10;5:117-24. doi: 10.2147/DDDT.S13029. [Article]
- Villanueva C, Bazan F, Kim S, Demarchi M, Chaigneau L, Thiery-Vuillemin A, Nguyen T, Cals L, Dobi E, Pivot X: Cabazitaxel: a novel microtubule inhibitor. Drugs. 2011 Jul 9;71(10):1251-8. doi: 10.2165/11591390-000000000-00000. [Article]
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Health Canada Approved Drug Products: CABAZITAXEL Intravenous Injection [Link]
- EMA Approved Drug Products: Jevtana (cabazitaxel) Intravenous Injection [Link]
- Biosynth Carbosynth: Cabazitaxel MSDS [Link]
- External Links
- Human Metabolome Database
- HMDB0015672
- KEGG Drug
- D09755
- PubChem Compound
- 9854073
- PubChem Substance
- 99443289
- ChemSpider
- 8029779
- 996051
- ChEBI
- 63584
- ChEMBL
- CHEMBL1201748
- ZINC
- ZINC000085536932
- PharmGKB
- PA165958401
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cabazitaxel
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Castration Resistant Prostate Cancer 1 somestatus stop reason just information to hide Not Available Completed Not Available Elderly Patients / Metastatic Prostate Cancer 1 somestatus stop reason just information to hide Not Available Completed Not Available Metastatic Castration Sensitive Prostate Cancer (mCSPC) / Metastatic Castration-Resistant Prostate Cancer (mCRPC) 1 somestatus stop reason just information to hide 4 Completed Treatment Metastatic Prostate Cancer 2 somestatus stop reason just information to hide 4 Completed Treatment Prostate Cancer 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 60 mg/1.5ml Injection, solution, concentrate Intravenous Kit; solution Intravenous 40 mg / mL Solution Intravenous 45 mg / 4.5 mL Solution Intravenous 60 mg / 6 mL Solution Parenteral 60 mg Injection Parenteral 60 MG Injection, solution, concentrate Intravenous 60 mg/1.5ml Injection, solution, concentrate Intravenous 10 MG/ML Injection, solution, concentrate Intravenous 20 mg/ml Solution, concentrate Intravenous 60 mg Injection Intravenous 60 MG/1.5ML Injection, solution, concentrate Intravenous; Parenteral 60 mg/1.5ml Injection, solution, concentrate; kit Intravenous 60 mg/1.5mL Solution Intravenous 40 mg / mL Solution Intravenous Injection Parenteral 60 mg/1.5ml Solution Intravenous 60 mg/1.5ml Injection, solution, concentrate Intravenous drip 60 mg/1.5ml Solution 60 mg/1.5ml Solution Intravenous 60 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5438072 No 1995-08-01 2014-05-22 US 
US5698582 No 1997-12-16 2012-07-03 US US6372780 No 2002-04-16 2016-03-26 US US6387946 No 2002-05-14 2016-03-26 US US8927592 Yes 2015-01-06 2031-04-27 US US7241907 Yes 2007-07-10 2026-06-10 US US5847170 Yes 1998-12-08 2021-09-26 US US6331635 No 2001-12-18 2016-03-26 US US10583110 No 2020-03-10 2030-10-27 US US10716777 No 2020-07-21 2030-10-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 170 https://datasheets.scbt.com/sds/eghs/en/sc-396754.pdf - Predicted Properties
Property Value Source Water Solubility 0.00413 mg/mL ALOGPS logP 3.69 ALOGPS logP 4.2 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 11.96 Chemaxon pKa (Strongest Basic) -3.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 202.45 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 213.4 m3·mol-1 Chemaxon Polarizability 86.25 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9535 Blood Brain Barrier - 0.9825 Caco-2 permeable - 0.7945 P-glycoprotein substrate Substrate 0.8287 P-glycoprotein inhibitor I Inhibitor 0.6646 P-glycoprotein inhibitor II Inhibitor 0.5887 Renal organic cation transporter Non-inhibitor 0.933 CYP450 2C9 substrate Non-substrate 0.8236 CYP450 2D6 substrate Non-substrate 0.882 CYP450 3A4 substrate Substrate 0.7256 CYP450 1A2 substrate Non-inhibitor 0.8197 CYP450 2C9 inhibitor Non-inhibitor 0.8654 CYP450 2D6 inhibitor Non-inhibitor 0.8935 CYP450 2C19 inhibitor Non-inhibitor 0.8429 CYP450 3A4 inhibitor Non-inhibitor 0.6339 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9068 Ames test Non AMES toxic 0.8028 Carcinogenicity Non-carcinogens 0.9264 Biodegradation Not ready biodegradable 0.9926 Rat acute toxicity 2.6378 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9907 hERG inhibition (predictor II) Non-inhibitor 0.7906
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 292.1316863 predictedDarkChem Lite v0.1.0 [M-H]- 293.0404863 predictedDarkChem Lite v0.1.0 [M-H]- 258.36423 predictedDeepCCS 1.0 (2019) [M+H]+ 291.2476863 predictedDarkChem Lite v0.1.0 [M+H]+ 291.6275863 predictedDarkChem Lite v0.1.0 [M+H]+ 260.08795 predictedDeepCCS 1.0 (2019) [M+Na]+ 290.7347863 predictedDarkChem Lite v0.1.0 [M+Na]+ 292.4353863 predictedDarkChem Lite v0.1.0 [M+Na]+ 266.63284 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin
- Specific Function
- GTP binding
- Gene Name
- TUBB1
- Uniprot ID
- Q9H4B7
- Uniprot Name
- Tubulin beta-1 chain
- Molecular Weight
- 50326.56 Da
References
- Nightingale G, Ryu J: Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. P T. 2012 Aug;37(8):440-8. [Article]
- Smiyun G, Azarenko O, Miller H, Rifkind A, LaPointe NE, Wilson L, Jordan MA: betaIII-tubulin enhances efficacy of cabazitaxel as compared with docetaxel. Cancer Chemother Pharmacol. 2017 Jul;80(1):151-164. doi: 10.1007/s00280-017-3345-2. Epub 2017 May 31. [Article]
- Zhu L, Zhang C, Lu X, Song C, Wang C, Zhang M, Xie Y, Schaefer HF 3rd: Binding modes of cabazitaxel with the different human beta-tubulin isotypes: DFT and MD studies. J Mol Model. 2020 May 30;26(6):162. doi: 10.1007/s00894-020-04400-w. [Article]
- DailyMed Label: JEVTANA (cabazitaxel) injection, for intravenous use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization (PubMed:30443021)
- Specific Function
- amyloid-beta binding
- Gene Name
- LDLR
- Uniprot ID
- P01130
- Uniprot Name
- Low-density lipoprotein receptor
- Molecular Weight
- 95375.105 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Binds also to a wide range of other molecules including Reelin/RELN or apolipoprotein E/APOE-containing ligands as well as clusterin/CLU (PubMed:24381170, PubMed:30873003). In the off-state of the pathway, forms homooligomers or heterooligomers with LRP8 (PubMed:30873003). Upon binding to ligands, homooligomers are rearranged to higher order receptor clusters that transmit the extracellular RELN signal to intracellular signaling processes by binding to DAB1 (PubMed:30873003). This interaction results in phosphorylation of DAB1 leading to the ultimate cell responses required for the correct positioning of newly generated neurons. Later, mediates a stop signal for migrating neurons, preventing them from entering the marginal zone (By similarity)
- Specific Function
- apolipoprotein binding
- Gene Name
- VLDLR
- Uniprot ID
- P98155
- Uniprot Name
- Very low-density lipoprotein receptor
- Molecular Weight
- 96097.45 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries (By similarity). Anchors LPL on the surface of endothelial cells in the lumen of blood capillaries (By similarity). Protects LPL against loss of activity, and against ANGPTL4-mediated unfolding (PubMed:27929370, PubMed:29899144). Thereby, plays an important role in lipolytic processing of chylomicrons by LPL, triglyceride metabolism and lipid homeostasis (PubMed:19304573, PubMed:21314738). Binds chylomicrons and phospholipid particles that contain APOA5 (PubMed:17997385, PubMed:19304573). Binds high-density lipoprotein (HDL) and plays a role in the uptake of lipids from HDL (By similarity)
- Specific Function
- acetylcholine receptor inhibitor activity
- Gene Name
- GPIHBP1
- Uniprot ID
- Q8IV16
- Uniprot Name
- Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
- Molecular Weight
- 19849.845 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Cabazitaxel inhibited this transporter in vitro; however, the in vivo risk of cabazitaxel inhibiting this transporter is low at the recommended therapeutic dose (25 mg/m^2).
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Cabazitaxel inhibited this transporter in vitro; however, the in vivo risk of cabazitaxel inhibiting this transporter is low at the recommended therapeutic dose (25 mg/m^2).
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Cabazitaxel inhibited this transporter in vitro; however, the in vivo risk of cabazitaxel inhibiting this transporter is low at the recommended therapeutic dose (25 mg/m^2).
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Cabazitaxel inhibited this transporter in vitro; however, the in vivo risk of cabazitaxel inhibiting this transporter is low at the recommended therapeutic dose (25 mg/m^2).
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: JEVTANA (cabazitaxel) injection, for intravenous use (June 2023) [Link]
Drug created at September 14, 2010 16:21 / Updated at April 23, 2024 11:38