Dasatinib hydrochloride (BMS-354825 HCl) (BMS-354825) hydrochloride is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib hydrochloride hydrochloride inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively. Dasatinib hydrochloride hydrochloride also induces Apoptosis and Autophagy.

c-Kit (WT):79 nM, Her2:710 nM, Src:0.8 nM, p38:100 nM, MEK:1700 nM, PDGFRβ:28 nM, FGFR1:880 nM, yes:0.5 nM, Her1:180 nM, Abl:0.6 nM, lck:0.4 nM, c-Kit (D816V):37 nM

Dasatinib hydrochloride demonstrates significant activity against Bcr-Abl, Src, Lck, Yes, c-Kit, PDGFRβ, p38, Her1, Her2, FGFR-1, and MEK with IC50s of <1.0, 0.50, 0.40, 0.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively. Dasatinib hydrochloride shows antiproliferative activities aversus K562 chronic myelogenous leukemia (CML), PC3 human prostate tumor, MDA-MB-231 human breast tumor, and WiDr human colon tumor cell lines with IC50s of <1.0 nM, 9.4 nM, 12 nM, and 52 nM, respectively[1].

Dasatinib hydrochloride (5 mg/kg and 50 mg/kg, qd×10d, 5 on-2 off) possesses potent antitumor activity and a high safety margin in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels. Dasatinib hydrochloride (10 mg/kg) has a pharmacokinetic profile appropriate for continued advancement into in vivo efficacy studies. Dasatinib hydrochloride (10 mg/kg) demonstrates favorable half-lives (t1/2s) of 3.3 and 3.1 h for i.v. and oral, respectively. The oral bioavailability (Fpo) in this study is 27%[1].