Masitinib(AB-1010)甲磺酸盐是新型的Kit，PDGFRα和β抑制剂，IC50分别为200 nM，540 nM和800 nM，对ABL和c-Fms抑制性较弱。
CAS：1048007-93-7
分子式：C29H34N6O4S2
分子量：594.75
纯度：98%
存储：Store at -20°C

Background:

Masitinib mesylate is a novel inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, and has weak inhibition to ABL and c-Fms. IC50: 200 nM (Kit), 540 nM (PDGFRα), 800 nM (PDGFRβ)

Masitinib is a competitive inhibitor against ATP at concentrations ≤500 nM. Masitinib also potently inhibits recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrates weak inhibition of Abl and c-Fms. Masitinib more strongly inhibits degranulation, cytokine production, and bone marrow mast cell migration than imatinib. In Ba/F3 cells expressing human wild-type Kit, masitinib inhibits SCF (stem cell factor)-induced cell proliferation with an IC50 of 150 nM, while the IC50 for inhibition of IL-3-stimulated proliferation is at approximately >10 µM. In Ba/F3 cells expressing PDGFRα, masitinib inhibits PDGF-BB-stimulated proliferation and PDGFRα tyrosine phosphorylation with IC50 of 300 nM. Masitinib also causes inhibition of SCF-stimulated tyrosine phosphorylation of human Kit in mastocytoma cell-lines and BMMC. Masitinib inhibits Kit gain-of-function mutants, including V559D mutant and δ27 mouse mutant with IC50 of 3 and 5 nM in Ba/F3 cells. Masitinib inhibits the cell proliferation of mastocytoma cell lines including HMC-1α155 and FMA3 with IC50 of 10 and 30 nM, respectively[1]. Masitinib inhibits cell growth and PDGFR phosphorylation in two novel ISS cell lines, which suggest that Masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS[2].

Masitinib inhibits tumour growth and increases the median survival time in δ27-expressing Ba/F3 tumor models at 30 mg/kg, without cardiotoxicity or genotoxicity[1]. Masitinib (12.5 mg/kg/d, p.o.) increases overall TTP (time-to-tumor progression) compared with placebo in dogs[3]. The combination of masitinib/gemcitabine shows synergy in vitro on proliferation of gemcitabine-refractory cell lines Mia Paca2 and Panc1, and to a lesser extent on Mia Paca-2 pancreatic tumours in mice[4].

[1]. Dubreuil P, et al. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLoS One, 2009, 4(9), e7258. [2]. Lawrence J, et al. Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Vet Comp Oncol, 2011, doi: 10.1111/j.1476-5829.2011.00291.x. [3]. Hahn KA, et al. Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med, 2008, 22(6), 1301-1309. [4]. Humbert M, et al. Masitinib combined with standard gemcitabine chemotherapy: in vitro and in vivo studies in human pancreatic tumour cell lines and ectopic mouse model. PLoS One. 2010 Mar 4;5(3):e9430.