中文名稱：Adagrasib
英文名稱：Adagrasib
CAS No.：2326521-71-3 分子式：C₃₂H₃₅ClFN₇O₂ 分子量：604.1174

產(chǎn)品活性：Asciminib (ABL001) hydrochloride 是一種有效和選擇性的變構(gòu) BCR-ABL1 抑制劑，抑制 Ba/F3 細(xì)胞生長(zhǎng)的 IC₅₀ 值為 0.25 nM。

研究領(lǐng)域：Protein Tyrosine Kinase/RTK

作用靶點(diǎn)：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.

In Vivo: Single doses of 7.5, 15 and 30 mg/kg Asciminib, administered to mice bearing KCL- 22 xenografts, inhibits pSTAT5 (Tyr694), which return to baseline at 10, 12 and 16-20 h after administration of the dose, respectively. In mice implanted with KCL-22 tumors, the minimum dose of Asciminib required for complete regression is 7.5 mg/kg twice a day (BID) or 30 mg/kg once a day (QD), and is tolerated at doses up to 250 mg/kg BID.