Dasatinib hydrochloride 是一种有效的 AblWT/Src 双重抑制剂，IC50 值分别为 0.6 nM/0.8 nM；同时抑制 c-KitWT/c-KitD816V，IC50 值分别为 79 nM/37 nM。
CAS：854001-07-3
分子式：C22H27Cl2N7O2S
分子量：524.47
纯度：98%
存储：Store at -20°C

Background:

Dasatinib hydrochloride is a potent and dual AblWT/Src inhibitor IC50 of 0.6 nM/0.8 nM respectively; also inhibits c-KitWT/c-KitD816V with IC50 of 79 nM/37 nM. IC50: 0.6 nM/0.8 nM (AblWT/Src)[1]IC50: 79 nM/37 nM (c-KitWT/c-KitD816V)[2]

Dasatinib potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range (IC50≤1.7 nM). Dasatinib (IC50: 0.8 nM) displays 325-fold greater potency compared with Imatinib against cells expressing wild-type Bcr-Abl in Ba/F3 cells[1].

Daily treatment with Dasatinib (50 mg/kg) is initiated on day 10. Using this approach, a significant inhibition of BCPAP orthotopic tumor growth is observed 6 days after treatment (day 16, P=0.014), which is sustained through days 23 and 29 (P=0.0003), compared with vehicle-treated mice[3]. Metabolism studies of Dasatinib (50 mg/kg) in rat suggested that Dasatinib is the major circulating component, whereas multiple metabolites contributed to the remaining 40-60% of the sample radioactivity at 4 h post dose[4].

[1]. O’Hare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. [2]. Shah NP, et al. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91. [3]. Chan CM, et al. Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis. Clin Cancer Res. 2012 Jul 1;18(13):3580-91. [4]. Shen Z, et al. Metabolite profiling of dasatinib dosed to Wistar Han rats using automated dried blood spot collection. J Pharm Biomed Anal. 2012 Aug-Sep;67-68:92-7.