Masitinib mesylate是一种生物口服可利用的选择性c-Kit抑制剂，IC50 为 200 nM。它还抑制PDGFRα/β，IC50值为540/800 nM，对 LynB 的IC50为510 nM。它的毒性低，有抗增殖和促凋亡活性。

Masitinib mesylate is a selective and orally bioavailable c-Kit inhibitor (IC50 of 200 nM,540/800 nM,510 nM for human recombinant c-Kit;PDGFRα/β;LynB,respectively).

In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200±40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50?of 150±80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain.?In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant[1].

Masitinib (12.5 mg/kg/d, p.o.) increases overall TTP (time-to-tumor progression) compared with placebo in dogs[2]

1048007-93-7

C29H34N6O4S2

594.75

甲磺酸马赛替尼;马赛替尼;AB-1010 mesylate

DMSO:25 mg/mL (42.03 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years