Identification

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Name
Axitinib
Accession Number
DB06626
Type
Small Molecule
Groups
Approved, Investigational
Description

Axitinib is a second generation tyrosine kinase inhibitor that works by selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3).7 Through this mechanism of action, axitinib blocks angiogenesis, tumour growth and metastases. It is reported to exhibit potency that is 50-450 times higher than that of the first generation VEGFR inhibitors.7 Axitinib is an indazole derivative.6 It is most commonly marketed under the name Inlyta® and is available in oral formulations.

Structure
Thumb
Synonyms
  • Axitinib
  • Axitinibum
External IDs
AG-013736 / AG-13736 / AG013736
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InlytaTablet, film coated1 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet, film coated1 mg/1OralU.S. Pharmaceuticals2012-01-27Not applicableUs
InlytaTablet, film coated7 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet, film coated5 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet, film coated1 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet7 mgOralPfizer Canada UlcNot applicableNot applicableCanada
InlytaTablet, film coated5 mg/1OralU.S. Pharmaceuticals2012-01-27Not applicableUs
InlytaTablet, film coated7 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet, film coated5 mgOralPfizer Europe Ma Eeig2012-09-03Not applicableEu
InlytaTablet3 mgOralPfizer Canada UlcNot applicableNot applicableCanada
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Categories
UNII
C9LVQ0YUXG
CAS number
319460-85-0
Weight
Average: 386.47
Monoisotopic: 386.120131908
Chemical Formula
C22H18N4OS
InChI Key
RITAVMQDGBJQJZ-FMIVXFBMSA-N
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+
IUPAC Name
N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide
SMILES
CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1

Pharmacology

Indication

Used in kidney cell cancer and investigated for use/treatment in pancreatic and thyroid cancer.

Associated Conditions
Pharmacodynamics

Axitinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.

Mechanism of action

Axitinib selectively blocks the tyrosine kinase receptors VEGFR-1 (vascular endothelial growth factor receptor), VEGFR-2, and VEGFR-3.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Humans
AVascular endothelial growth factor receptor 2
inhibitor
Humans
AVascular endothelial growth factor receptor 3
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

After one 5 mg dose of axitinib, it takes about 2.5 to 4.1 hours to reach maximum plasma concentration.

Volume of distribution

The volume of distribution is 160 L.

Protein binding

Plasma protein binding for axitinib is high at over 99% with most protein binding to albumin followed by α1-acid glycoprotein.

Metabolism

Axitinib undergoes mainly hepatic metabolism. CYP3A4 and CYP3A5 are the main hepatic enzymes while CYP1A2, CYP2C19, and UGT1A1 enzymes are secondary.

Route of elimination

Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. There is also 23% eliminated in the urine, most of which are metabolites.

Half life

Axitinib has a half life of 2.5 to 6.1 hours.

Clearance

The average clearance of axitinib is 38 L/h.

Toxicity

Some of the more serious toxic effects seen in patients taking axitinib include, but are not limited to, hypertension, thrombotic events, hemorrhage, and GI perforation.

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
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Axitinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Axitinib.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Axitinib.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Axitinib.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Axitinib.
8-azaguanineThe metabolism of Axitinib can be decreased when combined with 8-azaguanine.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Axitinib.
9-DeazaguanineThe metabolism of Axitinib can be decreased when combined with 9-Deazaguanine.
9-MethylguanineThe metabolism of Axitinib can be decreased when combined with 9-Methylguanine.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Axitinib.
Additional Data Available
  • Extended Description
    Extended Description

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

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  • 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.

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  • Action
    Action

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

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Food Interactions
  • Avoid combination with strong CYP3A4 inhibitors such as grapefruit juice due to the likely increased levels of axitinib. If the combination cannot be avoided, reduce axitinib dose by 50%.
  • Axitinib can be taken with or without food.

References

Synthesis Reference

Hu-Lowe D, Hallin M, Feeley R, Zou H, Rewolinski D, Wickman G, Chen E, Kim Y, Riney S, Reed J, Heller D, Simmons B, Kania R, McTigue M, Niesman M, Gregory S, Shalinsky D, Bender S. Characterization of potency and activity of the VEGF/PDGF receptor tyrosine kinase inhibitor AG013736. Proc Am Assoc Cancer Res. 2002;43:A5357.

General References
  1. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB: Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008 Oct 10;26(29):4708-13. doi: 10.1200/JCO.2007.15.9566. Epub 2008 Jun 9. [PubMed:18541897]
  2. Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004 Jul;165(1):35-52. [PubMed:15215160]
  3. Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G: Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 2005 Aug 20;23(24):5474-83. Epub 2005 Jul 18. [PubMed:16027439]
  4. Rini BI: SU11248 and AG013736: current data and future trials in renal cell carcinoma. Clin Genitourin Cancer. 2005 Dec;4(3):175-80. [PubMed:16425985]
  5. Gilbert JA, Adhikari LJ, Lloyd RV, Halfdanarson TR, Muders MH, Ames MM: Molecular markers for novel therapeutic strategies in pancreatic endocrine tumors. Pancreas. 2013 Apr;42(3):411-21. doi: 10.1097/MPA.0b013e31826cb243. [PubMed:23211371]
  6. Gross-Goupil M, Francois L, Quivy A, Ravaud A: Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. Clin Med Insights Oncol. 2013 Oct 29;7:269-77. doi: 10.4137/CMO.S10594. [PubMed:24250243]
  7. DRUG NAME: Axitinib - BC Cancer [Link]
External Links
KEGG Drug
D03218
PubChem Compound
6450551
PubChem Substance
347827779
ChemSpider
4953153
BindingDB
25117
ChEBI
66910
ChEMBL
CHEMBL1289926
PharmGKB
PA164924493
HET
AXI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Axitinib
ATC Codes
L01XE17 — Axitinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4ag8 / 4agc / 4twp / 4wa9
FDA label
Download (307 KB)
MSDS
Download (36.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdvanced Solid Tumors1
1Active Not RecruitingTreatmentHepatocellular,Carcinoma1
1Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
1CompletedNot AvailableHealthy Volunteers4
1CompletedTreatmentAdvanced Gastric Cancer / Stomach Neoplasms1
1CompletedTreatmentAdvanced Hepatocellular Carcinoma (HCC)1
1CompletedTreatmentAdvanced Solid Tumors2
1CompletedTreatmentCarcinoma NOS1
1CompletedTreatmentHepatic Insufficiency1
1CompletedTreatmentMalignancies1
1CompletedTreatmentMalignant Advanced Solid Tumors / Renal Cell Adenocarcinoma1
1CompletedTreatmentMetastatic Castrate-Resistant Prostate Cancer / Solid Malignancies1
1CompletedTreatmentNeoplasms3
1CompletedTreatmentRefractory or Recurrent Solid Tumors, Excluding CNS Tumors1
1CompletedTreatmentRenal Cell Adenocarcinoma1
1WithdrawnTreatmentAnaplastic Gliomas / Gliosarcoma / Recurrent Glioblastoma1
1WithdrawnTreatmentGlioblastomas / Hepatocellular,Carcinoma / Renal Cell Adenocarcinoma1
1, 2Active Not RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia (CML) / Blast Phase Chronic Myelogenous Leukemia (CML) / Chronic Phase Phase Chronic Myelogenous Leukemia (CML) / Leukemias / Philadelphia Chromosome Positive (Ph+) Phase Chronic Myelogenous Leukemia (CML)1
1, 2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentMalignant Pleural Mesothelioma (MPM)1
1, 2CompletedTreatmentNeoplasms, Breast1
1, 2CompletedTreatmentNeoplasms, Colorectal1
1, 2CompletedTreatmentRenal Cell Adenocarcinoma1
1, 2CompletedTreatmentTumors, Solid1
1, 2Not Yet RecruitingPreventionEndometriosis / Endometriosis Externa / Endometriosis Ovary / Endometriosis, Rectum1
1, 2RecruitingTreatmentAdvanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)1
1, 2RecruitingTreatmentLocally Advanced Non-Small Cell Lung Cancer / Metastatic Non-Small Cell Lung Cancer / Non-Small Cell Lung Cancer Stage IIIB1
1, 2RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS) / Soft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma1
2Active Not RecruitingTreatmentClear-cell Metastatic Renal Cell Carcinoma1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Urothelial Cancer1
2Active Not RecruitingTreatmentMalignant Melanoma / Melanoma / Stage IIIA Melanoma / Stage IIIB Melanoma / Stage IIIc Melanoma1
2Active Not RecruitingTreatmentMetastatic Malignant Neoplasm in Lymph Node / Prostate Cancer / Prostate Ductal Adenocarcinoma / Stage III Prostate Adenocarcinoma AJCC v7 / Stage IV Prostate Adenocarcinoma AJCC v71
2Active Not RecruitingTreatmentMetastatic Renal Cell Cancer1
2Active Not RecruitingTreatmentMetastatic Renal Cell Carcinoma1
2Active Not RecruitingTreatmentNeurofibromatosis Type 2 / Vestibular Schwannomas1
2Active Not RecruitingTreatmentPapillary Renal Cell Carcinoma1
2Active Not RecruitingTreatmentParaganglioma / Pheochromocytomas1
2Active Not RecruitingTreatmentRecurrent ACC, metastaticACC, Unreaectable ACC1
2Active Not RecruitingTreatmentRenal Cancers1
2Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentStage III Prostate Cancer / Stage IV Prostate Cancer1
2CompletedNot AvailableNeoplasms, Thyroid1
2CompletedTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentAdrenal Cortex Neoplasms1
2CompletedTreatmentAdvanced Renal Cell Carcinoma1
2CompletedTreatmentCarcinoid Tumors1
2CompletedTreatmentCarcinoma, Adenoid Cystic1
2CompletedTreatmentCarcinoma, Non-Small-Cell Lung (NSCLC)1
2CompletedTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2CompletedTreatmentHepatocellular,Carcinoma4
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Lung1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMelanoma / Skin Neoplasms1
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentNeoplasms, Colorectal1
2CompletedTreatmentNeoplasms, Kidney / Renal Cell Adenocarcinoma1
2CompletedTreatmentNeoplasms, Pancreatic1
2CompletedTreatmentNeoplasms, Thyroid1
2CompletedTreatmentRecurrent Glioblastoma (WHO-Grade IV Glioma)1
2CompletedTreatmentRecurrent or Metastatic NPC1
2CompletedTreatmentRenal Cell Adenocarcinoma3
2CompletedTreatmentSalivary Gland Cancers1
2CompletedTreatmentCT2a N0NxM0 Renal Tumor1
2Not Yet RecruitingTreatmentBiliary Tract Neoplasms / Hepatobiliary Neoplasms / Neoplasms, Hepatic1
2Not Yet RecruitingTreatmentMetastatic Adenoid Cystic Carcinoma / Progressive Disease / Recurrent Adenoid Cystic Carcinoma1
2Not Yet RecruitingTreatmentNeoadjuvant Therapy of Non-metastatic Locally Advanced Renal Cell Carcinoma1
2Not Yet RecruitingTreatmentSolitary Fibrous Tumor1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Metastatic Renal Cell Cancer / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer1
2RecruitingTreatmentMetastatic Renal Cell Carcinoma / Non-metastatic Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
2RecruitingTreatmentMetastatic Renal Cell Carcinoma / Renal Cell Carcinoma Associated With Xp11.2 Translocations/TFE3 Gene Fusions / Stage III Renal Cell Cancer AJCC v8 / Stage IV Renal Cell Cancer AJCC v8 / TFE3 Gene Translocation / TFEB Gene Translocation / Unresectable Renal Cell Carcinoma1
2RecruitingTreatmentParaganglioma / Pheochromocytomas1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentRenal Cell Adenocarcinoma1
2RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2TerminatedTreatmentCarcinoma, Colorectal1
2TerminatedTreatmentExtraocular Extension Melanoma / Metastatic Intraocular Melanoma / Recurrent Intraocular Melanoma / Recurrent Melanoma / Stage IIIA Intraocular Melanoma / Stage IIIA Melanoma / Stage IIIB Intraocular Melanoma / Stage IIIB Melanoma / Stage IIIC Intraocular Melanoma / Stage IIIc Melanoma / Stage IV Intraocular Melanoma / Stage IV Melanoma1
2TerminatedTreatmentMetastatic Renal Cell Carcinoma1
2TerminatedTreatmentRenal Cell Adenocarcinoma1
2Unknown StatusTreatmentGlioblastoma Multiforme (GBM)1
2Unknown StatusTreatmentNonclear Cell / Renal Cell Adenocarcinoma / Temsirolimus Resistance1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3Active Not RecruitingTreatmentCancer, Advanced / Neuroendocrine Tumors / Well-differentiated Non-pancreatic Neuroendocrine Carcinoma1
3Active Not RecruitingTreatmentNeoplasms, Kidney1
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma2
3CompletedTreatmentNeoplasms, Kidney1
3CompletedTreatmentPancreatic Ductal Carcinoma1
3RecruitingTreatmentAdvanced Melanoma1
3TerminatedPreventionClear Cell Renal Cell Carcinoma1
Not AvailableCompletedNot AvailableCarcinoma, Colorectal1
Not AvailableCompletedNot AvailableRenal Cell Adenocarcinoma1
Not AvailableNo Longer AvailableNot AvailableRenal Cell Adenocarcinoma1
Not AvailableNot Yet RecruitingNot AvailableCarcinoma NOS / Renal Cell1
Not AvailableRecruitingNot AvailableCarcinoma, Renal Cell, Advanced / Gastrointestinal Stroma Tumors / Mantle Cell Lymphoma (MCL)1
Not AvailableRecruitingTreatmentCervical Cancers1
Not AvailableRecruitingTreatmentTumors, Solid1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral3 mg
TabletOral5 mg
TabletOral7 mg
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral1 mg
Tablet, film coatedOral3 mg
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral5 mg
Tablet, film coatedOral7 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6534524No2003-03-182020-06-30Us
US7141581No2006-11-282020-06-30Us
US8791140No2014-07-292030-08-05Us
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 solubilityIn aqueous media with a pH between 1.1 to 7.8, axitinib has a solubility of over 0.2 μg/mL. From FDA label.
pKa4.8From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.000551 mg/mLALOGPS
logP4.17ALOGPS
logP4.15ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)13.07ChemAxon
pKa (Strongest Basic)4.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70.67 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity115.14 m3·mol-1ChemAxon
Polarizability42.58 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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/MSsplash10-052r-0129000000-7dcde0f91b9466cce9b4

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylthioethers. These are organosulfur compounds containing a thioether group that is substituted by two aryl groups.
Kingdom
Organic compounds
Super Class
Organosulfur compounds
Class
Thioethers
Sub Class
Aryl thioethers
Direct Parent
Diarylthioethers
Alternative Parents
O-sulfanylbenzoic acids and derivatives / Benzamides / Indazoles / Thiophenol ethers / Benzoyl derivatives / Vinylogous thioesters / Pyridines and derivatives / Pyrazoles / Heteroaromatic compounds / Secondary carboxylic acid amides
show 7 more
Substituents
Diarylthioether / O-sulfanylbenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Benzopyrazole / Indazole / Benzoyl / Thiophenol ether / Monocyclic benzene moiety / Pyridine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aryl sulfide, benzamides, pyridines, indazoles (CHEBI:66910)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB: Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008 Oct 10;26(29):4708-13. doi: 10.1200/JCO.2007.15.9566. Epub 2008 Jun 9. [PubMed:18541897]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB: Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008 Oct 10;26(29):4708-13. doi: 10.1200/JCO.2007.15.9566. Epub 2008 Jun 9. [PubMed:18541897]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB: Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008 Oct 10;26(29):4708-13. doi: 10.1200/JCO.2007.15.9566. Epub 2008 Jun 9. [PubMed:18541897]

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. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
  3. INLYTA® (axitinib) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
  3. INLYTA® (axitinib) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
  3. Axitinib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
  3. INLYTA® (axitinib) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
  3. INLYTA® (axitinib) FDA Label [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Chen Y, Tortorici MA, Garrett M, Hee B, Klamerus KJ, Pithavala YK: Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25. doi: 10.1007/s40262-013-0068-3. [PubMed:23677771]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC: 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. doi: 10.1007/s00228-011-1171-8. Epub 2011 Dec 15. [PubMed:22170007]
  2. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A: Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014 Feb 18;110(4):894-8. doi: 10.1038/bjc.2013.811. Epub 2014 Jan 7. [PubMed:24398510]

Drug created on March 19, 2008 10:41 / Updated on November 16, 2019 10:40