中文名称：Adagrasib 英文名称：AdagrasibCAS No.：2326521-71-3 分子式：C32H35ClFN7O2 分子量：604.1174
作用靶点：Bcr-Abl
In Vitro: Asciminib (ABL001) hydrochloride binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation.
Asciminib hydrochloride binds potently (dissociation constant=0.5-0.8 nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. Asciminib hydrochloride exhibits the same non-ATP-competitive biochemical kinetics as the BCRABL inhibitor GNF-2 but with approximately 100-fold greater potency.
Asciminib hydrochloride lacks activity against more than 60 kinases, including SRC, and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters.
In BCRABL1-transformed Ba/F3 cells grown without IL-3, Asciminib hydrochloride has an anti-proliferative with IC50 value of 0.25 nM. In the CML blast-phase cell line KCL-22, Asciminib hydrochloride inhibits phosphorylation of both STAT5 (Tyr694; pSTAT5) and BCRABL1 (Tyr245; pBCRABL1) after 1 h using concentrations that correlate with those required for inhibition of cell proliferation.
Asciminib hydrochloride is selectively active against all BCRABL1 lines (IC50 value of 120 nM), irrespective of the presence of either the p210 or the p190 BCRABL1 isoform.
