Axitinib

Drugbox
IUPAC_name = "N"-Methyl-2- [3- [("E")-2-pyridin-2-ylethenyl] -1"H"-indazol-6-yl] sulfanyl] benzamide

---

CAS_number = 319460-85-0
CAS_supplemental =
ATC_prefix =
ATC_suffix =
ATC_supplemental =
PubChem = 6450551
DrugBank =
chemical_formula =
C=22 | H=18 | N=4 | O=1 | S=1
molecular_weight = 386.469 g/mol
bioavailability =
protein_bound =
metabolism =
elimination_half-life =
excretion =
pregnancy_AU =
pregnancy_US =
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status =
routes_of_administration =

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 [Wilmes LJ, Pallavicini MG, Fleming LM, Gibbs J, Wang D, Li KL, Partridge SC, Henry RG, Shalinsky DR, Hu-Lowe D, Park JW, McShane TM, Lu Y, Brasch RC, Hylton NM. (2007) AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging. Magn Reson Imaging 25(3):319-27] and has been successful in trials with renal cell carcinoma (RCC) [Rini B, Rixe O, Bukowski R, Michaelson MD, Wilding G, Hudes G, Bolte O, Steinfeldt H, Reich SD, Motzer R. (2005) AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). ASCO Proceedings Abstract 4509] and several other tumor types [Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. (2005) Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 23(24):5474-83] .

A Phase II clinical trial showed good response in combination chemotherapy with Gemcitabine for advanced pancreatic cancer [Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. (2008) Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. [Epub ahead of print] ] . Currently, it is in Phase III clinical trials.

References