化合物 T15612

IC50: 2 nM (EML4-ALK G1202R, cell assay), 2 nM (EML4-ALK ^wt , cell assay), 2 nM (EML4-ALK C1156Y, cell assay), 2 nM (EML4-ALK F1174L, cell assay), 2 nM (EML4-ALK F1174L, cell assay)

JH-VIII-157-02 is a structural analogue of alectinib, acts as an ALK inhibitor, and shows an IC ₅₀ of 2 nM for echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) G1202R in cells. JH-VIII-157-02 also potently inhibits EML4-ALK ^wt (Eawt), EAC1156Y, EAF1174L, EAS1206Y (IC ₅₀ , 2 nM), EAG1269A (IC ₅₀ , 3 nM), EAL1196M (IC ₅₀ , 58 nM), EA1151Tins (IC ₅₀ , 107 nM), and EAL1152R (IC ₅₀ , 196 nM). Moreover, JH-VIII-157-02 has selectivity at other kinases, including IRAK1, CLK4, RET, RET V804L, RET V804M and IRAK 4, and the IC ₅₀ s are 14 nM, 14 nM, 3 nM, 13 nM, 12 nM, and 465 nM respectively. JH-VIII-157-02 exhibits inhibitory growth of cancer cell lines, such as H3122, DFCI76 (L1152R] with EC ₅₀ s of 5, 19 nM, respectively.

JH-VIII-157-02 exhibits good oral bioavailability following an oral dose of 10 mg/kg in mice. JH-VIII-157-02 also penetrates the CNS of mice.