Identification

Name
Cabozantinib
Accession Number
DB08875
Description

Cabozantinib was first approved in 2012 and is a non-specific tyrosine kinase inhibitor. It was initially approved in the US under the brand name Cometriq, which is indicated for the treatment of metastatic medullary thyroid cancer.6 In 2016, a capsule formulation (Cabometyx) was approved for the treatment of advanced renal cell carcinoma, and this same formulation gained additional approval in both the US and Canada in 2019 for the treatment of hepatocellular carcinoma in previously treated patients.7,8

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 501.514
Monoisotopic: 501.169999048
Chemical Formula
C28H24FN3O5
Synonyms
  • Cabozantinib
External IDs
  • BMS 907351
  • BMS907351
  • XL 184
  • XL-184
  • XL184

Pharmacology

Indication

Cabozantinib is indicated for the treatment of progressive, metastatic medullary thyroid cancer.6 It is also indicated for the treatment of advanced renal cell carcinoma and for hepatocellular carcinoma in patients previously treated with sorafenib.7,8

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases.

Mechanism of action

Cabozantinib inhibits specific receptor tyrosine kinases such as VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2.

TargetActionsOrganism
AHepatocyte growth factor receptor
antagonist
Humans
AVascular endothelial growth factor receptor 2
antagonist
Humans
AProto-oncogene tyrosine-protein kinase receptor Ret
antagonist
Humans
Absorption

After oral administration, peak plasma concentration was achieved in 2-5 hours.

Volume of distribution

The volume of distribution is 349L.

Protein binding

Cabozantinib has extensive plasma protein binding (≥ 99.7%).

Metabolism

Cabozantinib is metabolized mostly by CYP3A4 and, to a minor extent, by CYP2C9. Both enzyme produce an N-oxide metabolite.

Route of elimination

Cabozantinib is eliminated mostly by the feces (54%) and also by the urine (27%).

Half-life

Cabozantinib has a long half-life of 55 hours.

Clearance

At steady state, the clearance is 4.4 L/hr.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Cabozantinib carries a warning of serious gastrointestinal fistulas and perforations, and potentially fatal hemoptysis and gastrointestinal hemorrhage.

Affected organisms
  • Humans and other mammals
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
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Cabozantinib.
AbametapirThe serum concentration of Cabozantinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Cabozantinib can be increased when combined with Abatacept.
AbirateroneThe metabolism of Cabozantinib can be decreased when combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Cabozantinib.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Cabozantinib.
AcetohexamideThe metabolism of Cabozantinib can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazoleThe metabolism of Cabozantinib can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe metabolism of Cabozantinib can be decreased when combined with Acetylsalicylic acid.
AdalimumabThe metabolism of Cabozantinib can be increased when combined with Adalimumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase levels of cabozantinib.
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of cabozantinib.
  • Take on an empty stomach. Separate the administration of cabozantinib from food by at least 1 hour before or 2 hours after eating.
  • Take with a full glass of water.

Products

Product Ingredients
IngredientUNIICASInChI Key
Cabozantinib malateDR7ST46X581140909-48-3HFCFMRYTXDINDK-WNQIDUERSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CabometyxTablet40 mg/1OralExelixis, Inc.2016-04-25Not applicableUS flag
CabometyxTablet20 mgOralIpsen Biopharmaceuticals Canada Inc2018-10-10Not applicableCanada flag
CabometyxTablet60 mg/1OralExelixis, Inc.2016-04-25Not applicableUS flag
CabometyxTablet60 mgOralIpsen Biopharmaceuticals Canada Inc2018-10-10Not applicableCanada flag
CabometyxTablet20 mg/1OralExelixis, Inc.2016-04-25Not applicableUS flag
CabometyxTablet40 mgOralIpsen Biopharmaceuticals Canada Inc2018-10-10Not applicableCanada flag
CometriqCapsule20 mg/1OralCatalent Pharma Solutions, Llc2012-11-292018-01-19US flag
CometriqCapsule20 mgOralIpsen Pharma2014-03-20Not applicableEU flag
CometriqCapsule20 mg/1OralExelixis, Inc.2012-11-292012-12-04US flag
CometriqCapsule20 mg/1OralExelixis, Inc.2012-11-29Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CometriqCabozantinib malate (20 mg/1) + Cabozantinib malate (80 mg/1)KitOralCatalent Pharma Solutions, Llc2012-11-292018-01-19US flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)OralExelixis, Inc.2012-11-29Not applicableUS flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)KitOralCatalent Pharma Solutions, Llc2012-11-292018-01-19US flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)OralExelixis, Inc.2012-11-29Not applicableUS flag
CometriqCabozantinib malate (20 mg/1) + Cabozantinib malate (80 mg/1)KitOralCatalent Pharma Solutions, Llc2012-11-292018-01-19US flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)OralExelixis, Inc.2012-11-29Not applicableUS flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)OralExelixis, Inc.2012-11-29Not applicableUS flag
CometriqCabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1)KitOralCatalent Pharma Solutions, Llc2012-11-292018-01-19US flag

Categories

ATC Codes
L01XE26 — Cabozantinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Quinolines and derivatives / Anilides / Phenoxy compounds / Anisoles / N-arylamides / Alkyl aryl ethers / Fluorobenzenes / Pyridines and derivatives / Aryl fluorides / Cyclopropanecarboxylic acids and derivatives
show 8 more
Substituents
Alkyl aryl ether / Anilide / Anisole / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, dicarboxylic acid diamide, aromatic ether, quinolines (CHEBI:72317)

Chemical Identifiers

UNII
1C39JW444G
CAS number
849217-68-1
InChI Key
ONIQOQHATWINJY-UHFFFAOYSA-N
InChI
InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
IUPAC Name
N'1-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
SMILES
COC1=CC2=C(C=C1OC)C(OC1=CC=C(NC(=O)C3(CC3)C(=O)NC3=CC=C(F)C=C3)C=C1)=CC=N2

References

General References
  1. Durante C, Russo D, Verrienti A, Filetti S: XL184 (cabozantinib) for medullary thyroid carcinoma. Expert Opin Investig Drugs. 2011 Mar;20(3):407-413. doi: 10.1517/13543784.2011.559163. [PubMed:21314233]
  2. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25. [PubMed:26406150]
  3. Krajewska J, Olczyk T, Jarzab B: Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer. Expert Rev Clin Pharmacol. 2016;9(1):69-79. doi: 10.1586/17512433.2016.1102052. Epub 2015 Nov 4. [PubMed:26536165]
  4. Grullich C: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res. 2014;201:207-14. doi: 10.1007/978-3-642-54490-3_12. [PubMed:24756794]
  5. Escudier B, Lougheed JC, Albiges L: Cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2016 Dec;17(18):2499-2504. doi: 10.1080/14656566.2016.1258059. Epub 2016 Nov 22. [PubMed:27835047]
  6. FDA Approved Drug Products: Cometriq (cabozantinib) oral capsules [Link]
  7. FDA Approved Drug Products: Cabometyx (cabozantinib) oral tablets [Link]
  8. Health Canada Product Monograph: Cabometyx (cabozantinib) oral tablets [Link]
KEGG Drug
D10062
PubChem Compound
25102847
PubChem Substance
347827806
ChemSpider
25948202
BindingDB
50021574
RxNav
1363268
ChEBI
72317
ChEMBL
CHEMBL2105717
ZINC
ZINC000070466416
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cabozantinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (194 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMedullary Thyroid Cancer (MTC)1
4RecruitingTreatmentHepatocellular Carcinoma1
3Active Not RecruitingTreatmentHepatocellular Carcinoma1
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma2
3Active Not RecruitingTreatmentThyroid Cancers1
3CompletedTreatmentCastration Resistant Prostate Cancer (CRPC) / Castration-Resistant Prostate Cancer (CRPC) / Pain / Prostate Cancer / Prostatic Neoplasms1
3RecruitingTreatmentAdenocarcinoma, Prostate / Metastatic Hormone Refractory Prostate Cancer1
3RecruitingTreatmentAtypical Carcinoid Tumor / Carcinoid Tumors / Functioning Pancreatic Neuroendocrine Tumor / Intermediate Grade Lung Neuroendocrine Neoplasm / Locally Advanced Pancreatic Neuroendocrine Tumor / Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm / Low Grade Lung Neuroendocrine Neoplasm / Lung Atypical Carcinoid Tumor / Lung Carcinoid Tumor / Metastatic Digestive System Neuroendocrine Neoplasm / Metastatic Digestive System Neuroendocrine Tumor G1 / Metastatic Pancreatic Neuroendocrine Tumors / Metastatic Thymic Neuroendocrine Neoplasm / Neuroendocrine Neoplasms / Non-Functioning Pancreatic Neuroendocrine Tumor / Pancreatic Serotonin-Producing Neuroendocrine Tumor / Stage IIIA Digestive System Neuroendocrine Tumor AJCC v7 / Stage IIIB Digestive System Neuroendocrine Tumor AJCC v7 / Stage IV Digestive System Neuroendocrine Tumor AJCC v71
3RecruitingTreatmentClear Cell Renal Cell Carcinoma / Metastatic Malignant Neoplasm in Lymph Node / Metastatic Malignant Neoplasm in the Bone / Metastatic Malignant Neoplasm in the Soft Tissues / Metastatic Malignant Neoplasm in the Viscera / Sarcomatoid Renal Cell Carcinoma / Stage IV Renal Cell Cancer AJCC v81
3RecruitingTreatmentDifferentiated Thyroid Cancer (DTC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral20 mg/1
TabletOral20 mg
TabletOral40 mg/1
TabletOral40 mg
TabletOral60 mg
TabletOral60 mg/1
Tablet, film coatedOral20 MG
Tablet, film coatedOral40 MG
Tablet, film coatedOral60 MG
Tablet, coated20 mg
Tablet, coated40 mg
Tablet, coated60 mg
CapsuleOral20 mg
CapsuleOral20 mg/1
KitOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8877776No2014-11-042030-10-08US flag
US7579473No2009-08-252024-09-24US flag
US8497284No2013-07-302024-09-24US flag
US9724342No2017-08-082033-07-09US flag
US9717720No2017-08-012032-02-10US flag
US10039757No2018-08-072031-07-18US flag
US10034873No2018-07-312031-07-18US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityCOMETRIQ is practically insoluble in water.From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.00199 mg/mLALOGPS
logP4.01ALOGPS
logP4.66ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)13.46ChemAxon
pKa (Strongest Basic)5.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area98.78 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity136.12 m3·mol-1ChemAxon
Polarizability51.49 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0139180000-20096332e7e989d72392

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name
MET
Uniprot ID
P08581
Uniprot Name
Hepatocyte growth factor receptor
Molecular Weight
155540.035 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]
  2. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [PubMed:21926191]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]
  2. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [PubMed:21926191]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [PubMed:21606412]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Nguyen L, Holland J, Miles D, Engel C, Benrimoh N, O'Reilly T, Lacy S: Pharmacokinetic (PK) drug interaction studies of cabozantinib: Effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK. J Clin Pharmacol. 2015 Sep;55(9):1012-23. doi: 10.1002/jcph.510. Epub 2015 Jun 2. [PubMed:25854986]
  2. Gerendash BS, Creel PA: Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064. doi: 10.2147/OTT.S145295. eCollection 2017. [PubMed:29089775]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Cabozantinib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Escudier B, Lougheed JC, Albiges L: Cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2016 Dec;17(18):2499-2504. doi: 10.1080/14656566.2016.1258059. Epub 2016 Nov 22. [PubMed:27835047]

Drug created on May 12, 2013 18:12 / Updated on September 25, 2020 15:13

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