Details of the Drug

General Information of Drug (ID: DMGVH6N)

Drug Name

Axitinib

Synonyms

AG 013736; AG013736; AG-013736; AG-13736; AG-013736, Axitinib; N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide; N-methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide; Axitinib (VEGFR inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Approved	[1]

Therapeutic Class

Anticancer Agents

Affected Organisms

Humans and other mammals

ATC Code

L01EK01: Axitinib

L01EK: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors

L01E: PROTEIN KINASE INHIBITORS

L01: ANTINEOPLASTIC AGENTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

386.5

Logarithm of the Partition Coefficient (xlogp)

4.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Clearance: The drug present in the plasma can be removed from the body at the rate of 5 mL/min/kg [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 4.3 hours [3]
Unbound Fraction: The unbound fraction of drug in plasma is 0.004% [3]

Chemical Identifiers

Formula: C22H18N4OS
IUPAC Name: N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide
Canonical SMILES: CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)/C=C/C4=CC=CC=N4
InChI: InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+
InChIKey: RITAVMQDGBJQJZ-FMIVXFBMSA-N

Cross-matching ID

PubChem CID: 6450551
ChEBI ID: CHEMBL66910
CAS Number: 319460-85-0
UNII: C9LVQ0YUXG
DrugBank ID: DB06626
TTD ID: D01ZRI
VARIDT ID: DR00035
INTEDE ID: DR0162
ACDINA ID: D00053

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[5]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[7]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[7]

Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Renal cell carcinoma

ICD Disease Classification

2C90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DTP	OATP1B1	8.15E-01	6.20E-03	5.61E-02
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	1.10E-01	-5.91E-02	-3.60E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.36E-01	1.62E-02	1.08E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.96E-01	-3.17E-03	-1.84E-02
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	2.40E-01	-3.31E-02	-1.97E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Axitinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Axitinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[8]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Axitinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Major	Increased metabolism of Axitinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Axitinib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[10]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Axitinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
Tucatinib	DMBESUA	Major	Decreased metabolism of Axitinib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[8]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Axitinib caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[11]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Axitinib caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[9]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Axitinib caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[11]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Axitinib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[11]
SODIUM CITRATE	DMHPD2Y	Minor	Decreased absorption of Axitinib due to altered gastric pH caused by SODIUM CITRATE.	Discovery agent [N.A.]	[12]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Axitinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Axitinib and Cannabidiol.	Epileptic encephalopathy [8A62]	[11]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Axitinib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[9]
Boceprevir	DMBSHMF	Major	Decreased metabolism of Axitinib caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[8]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Axitinib and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[13]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Axitinib caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[8]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Axitinib and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[14]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Axitinib and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[15]
Levamlodipine	DM92S6N	Moderate	Decreased metabolism of Axitinib caused by Levamlodipine mediated inhibition of CYP450 enzyme.	Hypertension [BA00-BA04]	[11]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Axitinib caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[9]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Axitinib caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[11]
Suvorexant	DM0E6S3	Moderate	Decreased metabolism of Axitinib caused by Suvorexant mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[11]
Crizotinib	DM4F29C	Moderate	Decreased metabolism of Axitinib caused by Crizotinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Ceritinib	DMB920Z	Major	Decreased metabolism of Axitinib caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[8]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Axitinib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Axitinib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[16]
Idelalisib	DM602WT	Major	Decreased metabolism of Axitinib caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[8]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Axitinib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[11]
Vemurafenib	DM62UG5	Moderate	Increased metabolism of Axitinib caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[9]
Dabrafenib	DMX6OE3	Major	Increased metabolism of Axitinib caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[9]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Axitinib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[11]
Netupitant	DMEKAYI	Moderate	Decreased metabolism of Axitinib caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[11]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of Axitinib caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[11]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Axitinib caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[11]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Axitinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[17]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Axitinib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[18]
Enzalutamide	DMGL19D	Major	Increased metabolism of Axitinib caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[9]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Axitinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[11]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Axitinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[11]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Axitinib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
LEE011	DMMX75K	Moderate	Decreased metabolism of Axitinib caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Axitinib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[19]
Brilinta	DMBR01X	Moderate	Decreased metabolism of Axitinib caused by Brilinta mediated inhibition of CYP450 enzyme.	Thrombosis [DB61-GB90]	[11]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Axitinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]


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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent


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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Axitinib 1 mg tablet	1 mg	Oral Tablet	Oral
Axitinib 5 mg tablet	5 mg	Oral Tablet	Oral

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5659).
2	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
5	Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol. 2012 May;68(5):645-55.
6	Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25.
7	MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.
8	Cerner Multum, Inc. "Australian Product Information.".
9	Pithavala YK, Tortorici M, Toh M, et al "Effect of rifampin on the pharmacokinetics of axitinib (AG-013736) in Japanese and Caucasian healthy volunteers." Cancer Chemother Pharmacol 65 (2010): 563-70. [PMID: 19603168]
10	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
11	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
12	Product Information. Inlyta (axitinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
13	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
14	Canadian Pharmacists Association.
15	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
16	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
17	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
18	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
19	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.