Identification

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

Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3. Axitinib is marketed under the name Inlyta®, and if one previous systemic therapy for kidney cell cancer has failed, axitinib is indicated.

Structure
Thumb
Synonyms
  • axitinib
  • axitinibum
External IDs
AG-013736 / AG-13736 / AG013736
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InlytaTablet, film coated1 mg/1OralU.S. Pharmaceuticals2012-01-27Not applicableUs
InlytaTablet, film coated1 mgOralPfizer2012-09-03Not applicableEu
InlytaTablet, film coated3 mgOralPfizer2012-09-03Not applicableEu
InlytaTablet, film coated7 mgOralPfizer2012-09-03Not applicableEu
InlytaTablet5 mgOralPfizer2012-08-17Not applicableCanada
InlytaTablet, film coated5 mgOralPfizer2012-09-03Not applicableEu
InlytaTablet, film coated1 mgOralPfizer2012-09-03Not applicableEu
InlytaTablet, film coated1 mg/1OralPfizer Laboratories Div Pfizer Inc.2012-01-27Not applicableUs
InlytaTablet, film coated5 mg/1OralU.S. Pharmaceuticals2012-01-27Not applicableUs
InlytaTablet, film coated5 mgOralPfizer2012-09-03Not applicableEu
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]-2H-indazol-6-yl}sulfanyl)benzene-1-carboximidic acid
SMILES
[H]\C(=C(\[H])C1=CC=CC=N1)C1=C2C=CC(SC3=CC=CC=C3C(O)=NC)=CC2=NN1

Pharmacology

Indication

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

Structured Indications
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
Human
AVascular endothelial growth factor receptor 2
inhibitor
Human
AVascular endothelial growth factor receptor 3
inhibitor
Human
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
DrugInteractionDrug group
AbirateroneThe serum concentration of Axitinib can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Axitinib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Axitinib.Experimental
AmiodaroneThe serum concentration of Axitinib can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Axitinib can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Axitinib can be decreased when combined with Armodafinil.Approved, Investigational
AtazanavirThe serum concentration of Axitinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Axitinib can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Axitinib can be decreased when combined with Azithromycin.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Axitinib.Approved, Investigational
BoceprevirThe serum concentration of Axitinib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Axitinib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Axitinib can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Axitinib.Approved
CaffeineThe metabolism of Axitinib can be decreased when combined with Caffeine.Approved
CarbamazepineThe serum concentration of Axitinib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Axitinib can be increased when it is combined with Ceritinib.Approved
ChloramphenicolThe metabolism of Axitinib can be decreased when combined with Chloramphenicol.Approved, Vet Approved
CholecalciferolThe metabolism of Axitinib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Axitinib can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Axitinib can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Axitinib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Axitinib can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Axitinib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Axitinib can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Axitinib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Axitinib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Axitinib.Approved, Investigational
CyclosporineThe metabolism of Axitinib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Axitinib.Experimental
Cyproterone acetateThe serum concentration of Axitinib can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Axitinib can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Axitinib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Axitinib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Axitinib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Axitinib can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Axitinib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Axitinib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Axitinib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Axitinib.Approved
DihydroergotamineThe metabolism of Axitinib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Axitinib can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Axitinib.Approved, Investigational
DosulepinThe metabolism of Axitinib can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Axitinib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Axitinib can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Axitinib can be decreased when combined with Efavirenz.Approved, Investigational
EltrombopagThe serum concentration of Axitinib can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Axitinib can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Axitinib can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Axitinib can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Axitinib can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe metabolism of Axitinib can be decreased when combined with Etravirine.Approved
FluconazoleThe metabolism of Axitinib can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Axitinib can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Axitinib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Axitinib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Axitinib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Axitinib can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Axitinib can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Axitinib can be decreased when combined with Gemfibrozil.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Axitinib.Experimental
IdelalisibThe serum concentration of Axitinib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Axitinib can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Axitinib can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Axitinib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Axitinib can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Axitinib can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Axitinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Axitinib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Axitinib can be increased when it is combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Axitinib.Experimental
LidocaineThe metabolism of Axitinib can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Axitinib can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe serum concentration of Axitinib can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Axitinib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Axitinib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Axitinib can be decreased when it is combined with Lumacaftor.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Axitinib.Experimental
MexiletineThe metabolism of Axitinib can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Axitinib can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Axitinib can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Axitinib can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Axitinib can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Axitinib can be decreased when combined with Modafinil.Approved, Investigational
NefazodoneThe serum concentration of Axitinib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Axitinib can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Axitinib can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Axitinib can be decreased when it is combined with Nevirapine.Approved
NicardipineThe metabolism of Axitinib can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Axitinib can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Axitinib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Axitinib.Experimental, Investigational
OmeprazoleThe metabolism of Axitinib can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Axitinib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Axitinib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Axitinib.Approved, Vet Approved
PalbociclibThe serum concentration of Axitinib can be increased when it is combined with Palbociclib.Approved
PantoprazoleThe metabolism of Axitinib can be decreased when combined with Pantoprazole.Approved
Peginterferon alfa-2bThe serum concentration of Axitinib can be increased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe serum concentration of Axitinib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Axitinib.Experimental
PhenobarbitalThe serum concentration of Axitinib can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Axitinib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe serum concentration of Axitinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Axitinib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Axitinib.Experimental
RanolazineThe serum concentration of Axitinib can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Axitinib can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Axitinib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Axitinib can be decreased when it is combined with Rifapentine.Approved
RopiniroleThe metabolism of Axitinib can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe serum concentration of Axitinib can be increased when it is combined with Saquinavir.Approved, Investigational
SertralineThe metabolism of Axitinib can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Axitinib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Axitinib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Axitinib can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Axitinib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Axitinib can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Axitinib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Axitinib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Axitinib can be increased when it is combined with Telithromycin.Approved
Tenofovir disoproxilThe metabolism of Axitinib can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Axitinib can be increased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Axitinib can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Axitinib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Axitinib can be decreased when it is combined with Tocilizumab.Approved
TopiramateThe metabolism of Axitinib can be decreased when combined with Topiramate.Approved
TranylcypromineThe metabolism of Axitinib can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Axitinib.Approved, Investigational
VenlafaxineThe metabolism of Axitinib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Axitinib can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Axitinib can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Axitinib can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Axitinib can be decreased when combined with Zucapsaicin.Approved
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]
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 RecruitingTreatmentRefractory or Recurrent Solid Tumors, Excluding CNS Tumors1
1Active Not RecruitingTreatmentRenal Cell Adenocarcinoma2
1CompletedNot AvailableHealthy Volunteers4
1CompletedTreatmentAdvanced Gastric Cancer / Stomach Neoplasms1
1CompletedTreatmentAdvanced Solid Tumors2
1CompletedTreatmentCancers1
1CompletedTreatmentCarcinoma NOS1
1CompletedTreatmentHepatic Insufficiency1
1CompletedTreatmentMetastatic Castrate-Resistant Prostate Cancer / Solid Malignancies1
1CompletedTreatmentNeoplasms3
1RecruitingTreatmentAdvanced Hepatocellular Carcinoma (HCC)1
1RecruitingTreatmentAdvanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)1
1RecruitingTreatmentHepatocellular,Carcinoma1
1SuspendedTreatmentAnaplastic Gliomas / Gliosarcoma / Recurrent Glioblastoma1
1, 2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
1, 2CompletedTreatmentMalignant Pleural Mesothelioma (MPM)1
1, 2CompletedTreatmentNeoplasms, Breast1
1, 2CompletedTreatmentNeoplasms, Colorectal1
1, 2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1, 2Enrolling by InvitationTreatmentTumors, Solid1
1, 2RecruitingTreatmentClear Cell Renal Cell Carcinoma1
1, 2RecruitingTreatmentLeukemias1
1, 2RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentCarcinoid Tumors1
2Active Not RecruitingTreatmentGlioblastoma Multiforme1
2Active Not RecruitingTreatmentHepatocellular,Carcinoma3
2Active Not RecruitingTreatmentMalignant Melanoma / Melanoma / Stage IIIA Melanoma / Stage IIIB Melanoma / Stage IIIc Melanoma1
2Active Not RecruitingTreatmentParaganglioma / Pheochromocytomas1
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
2CompletedTreatmentCarcinoma, Adenoid Cystic1
2CompletedTreatmentCarcinoma, Non-Small-Cell Lung (NSCLC)1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMelanoma / Skin Neoplasms1
2CompletedTreatmentNeoplasms, Colorectal1
2CompletedTreatmentNeoplasms, Kidney / Renal Cell Adenocarcinoma1
2CompletedTreatmentNeoplasms, Lung / Non-Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentNeoplasms, Pancreatic1
2CompletedTreatmentNeoplasms, Thyroid1
2CompletedTreatmentRecurrent or Metastatic NPC1
2CompletedTreatmentRenal Cell Adenocarcinoma3
2CompletedTreatmentCT2a N0NxM0 Renal Tumor1
2Not Yet RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentRenal Cell Adenocarcinoma1
2Not Yet RecruitingTreatmentSolitary Fibrous Tumor1
2RecruitingTreatmentAdvanced Renal Cell Carcinoma1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS) / Soft Tissue Sarcoma (STS)1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Metastatic Renal Cell Cancer / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
2RecruitingTreatmentMetastatic Renal Cell Cancer1
2RecruitingTreatmentMetastatic Renal Cell Carcinoma1
2RecruitingTreatmentNeurofibromatosis Type 2 / Vestibular Schwannomas1
2RecruitingTreatmentPapillary Renal Cell Carcinoma1
2RecruitingTreatmentProstate Cancer1
2RecruitingTreatmentRecurrent ACC, metastaticACC, Unreaectable ACC1
2RecruitingTreatmentRecurrent Glioblastoma (WHO-Grade IV Glioma)1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentSalivary Gland Cancers1
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 StatusTreatmentClear-cell Metastatic Renal Cell Carcinoma1
2Unknown StatusTreatmentGlioblastoma Multiforme1
2Unknown StatusTreatmentNonclear Cell / Renal Cell Adenocarcinoma / Temsirolimus Resistance1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3RecruitingTreatmentCancer, Advanced / Neuroendocrine Tumors / Well-differentiated Non-pancreatic Neuroendocrine Carcinoma1
3Active Not RecruitingPreventionClear Cell Renal Cell Carcinoma1
3Active Not RecruitingTreatmentNeoplasms, Kidney1
3CompletedTreatmentNeoplasms, Kidney1
3CompletedTreatmentPancreatic Ductal Carcinoma1
3RecruitingTreatmentRenal Cell Adenocarcinoma2
Not AvailableActive Not RecruitingTreatmentTumors, Solid1
Not AvailableCompletedNot AvailableCarcinoma, Colorectal1
Not AvailableCompletedNot AvailableRenal Cell Adenocarcinoma1
Not AvailableNo Longer AvailableNot AvailableRenal Cell Adenocarcinoma1
Not AvailableNot Yet RecruitingNot AvailableAdvanced Renal Cell Carcinoma1
Not AvailableRecruitingNot AvailableCarcinoma, Renal Cell, Advanced / Gastrointestinal Stroma Tumors / Lymphoma, Mantle-Cell1

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
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral7 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6534524No2000-06-302020-06-30Us
US7141581No2000-06-302020-06-30Us
US8791140No2010-08-052030-08-05Us

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 Solubility0.000511 mg/mLALOGPS
logP4.56ALOGPS
logP5.01ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)7.73ChemAxon
pKa (Strongest Basic)5.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity115.73 m3·mol-1ChemAxon
Polarizability42.71 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
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
Human
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
Human
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
Human
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
Human
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]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]

Transporters

Kind
Protein
Organism
Human
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
Human
Pharmacological action
No
Actions
Substrate
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]

Drug created on March 19, 2008 10:41 / Updated on November 22, 2017 12:36