Description: Axitinib, also known as AG013736, is an orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect. A xitinib has received FDA (27 January 2012), EMA (13 September 2012), MHRA (3 September 2012) and TGA (26 July 2012) approval for use as a treatment for renal cell carcinoma. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
Synonym: AG013736; AG 013736; AG-013736; Brand name: Inlyta.
IUPAC/Chemical Name: (E)-N-methyl-2-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)benzamide
MedKoo Cat#: 200400
Chemical Formula: C22H18N4OS
Exact Mass: 386.12013
Molecular Weight: 386.47
Elemental Analysis: C, 68.37; H, 4.69; N, 14.50; O, 4.14; S, 8.30
Axitinib (also known as AG013736) is a small molecule tyrosine kinase inhibitor under development by Pfizer. It inhibits multiple targets, including VEGFR-1, VEGFR-2, VEGFR-3, platelet derived growth factor receptor (PDGFR), and cKIT (CD117). It has been shown to significantly inhibit growth of breast cancer in xenograft models and has been successful in trials with renal cell carcinoma (RCC) and several other tumor types.
Axitinib is a white to light-yellow powder with a pKa of 4.8. The solubility of axitinib in aqueous media over the range pH 1.1 to pH 7.8 is in excess of 0.2 μg/mL. The partition coefficient (n-octanol/water) is 3.5.
A Phase II clinical trial showed good response in combination chemotherapy with Gemcitabine for advanced pancreatic cancer. However, Pfizer reported on January 30, 2009 that Phase III clinical trials of the drug when used in combination with Gemcitabine showed no evidence of improved survival rates over treatments using Gemcitabine alone for advanced pancreatic cancer and halted the trial. see http://en.wikipedia.org/wiki/Axitinib.
1: Gunnarsson O, Pfanzelter NR, Cohen RB, Keefe SM. Evaluating the safety and efficacy of axitinib in the treatment of advanced renal cell carcinoma. Cancer Manag Res. 2015 Feb 11;7:65-73. doi: 10.2147/CMAR.S74202. eCollection 2015. Review. PubMed PMID: 25709499; PubMed Central PMCID: PMC4334173.
2: Tzogani K, Skibeli V, Westgaard I, Dalhus M, Thoresen H, Slot KB, Damkier P, Hofland K, Borregaard J, ErsbÃ¸ll J, Salmonson T, Pieters R, Sylvester R, Mickisch G, Bergh J, Pignatti F. The European Medicines Agency Approval of Axitinib (Inlyta) for the Treatment of Advanced Renal Cell Carcinoma After Failure of Prior Treatment With Sunitinib or a Cytokine: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. Oncologist. 2015 Feb;20(2):196-201. Epub 2015 Jan 23. Review. PubMed PMID: 25616431; PubMed Central PMCID: PMC4319625.
3: Borst DL, Arruda LS, MacLean E, Pithavala YK, Morgado JE. Common questions regarding clinical use of axitinib in advanced renal cell carcinoma. Am J Health Syst Pharm. 2014 Jul 1;71(13):1092-6. doi: 10.2146/ajhp130581. Review. PubMed PMID: 24939498.
4: Verzoni E, Grassi P, Testa I, Iacovelli R, Biondani P, Garanzini E, De Braud F, Procopio G. Targeted treatments in advanced renal cell carcinoma: focus on axitinib. Pharmgenomics Pers Med. 2014 Mar 27;7:107-16. doi: 10.2147/PGPM.S37098. eCollection 2014. Review. PubMed PMID: 24715765; PubMed Central PMCID: PMC3977458.
5: Bracarda S, Castellano D, Procopio G, SepÃºlveda JM, Sisani M, Verzoni E, Schmidinger M. Axitinib safety in metastatic renal cell carcinoma: suggestions for daily clinical practice based on case studies. Expert Opin Drug Saf. 2014 Apr;13(4):497-510. doi: 10.1517/14740338.2014.888413. Review. PubMed PMID: 24641566.
6: Akaza H, Fukuyama T. Axitinib for the treatment of advanced renal cell carcinoma. Expert Opin Pharmacother. 2014 Feb;15(2):283-97. doi: 10.1517/14656566.2014.868436. Epub 2013 Dec 13. Review. PubMed PMID: 24328549.
7: Gross-Goupil M, FranÃ§ois 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. Review. PubMed PMID: 24250243; PubMed Central PMCID: PMC3825605.
8: 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. Review. PubMed PMID: 23677771.
9: Qi WX, He AN, Shen Z, Yao Y. Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis. Br J Clin Pharmacol. 2013 Sep;76(3):348-57. doi: 10.1111/bcp.12149. Review. PubMed PMID: 23617405; PubMed Central PMCID: PMC3769663.
10: King JW, Lee SM. Axitinib for the treatment of advanced non-small-cell lung cancer. Expert Opin Investig Drugs. 2013 Jun;22(6):765-73. doi: 10.1517/13543784.2013.775243. Epub 2013 Mar 1. Review. PubMed PMID: 23452008.