ALK-IN-1 (AP26113) is a potent ALK inhibitor with IC50 of 0.62 nM in a cell-free assay, demonstrated ability overcome Crizotinib resistance mediated by a L1196M mutation. Phase 2.

ALK:0.62 nM

In HCC827 (EGFR-DEL) or HCC827 (EGFR-DEL/T790M) transplantation tumor mouse models, AP26113 (25 mg/kg), inhibited tumor cell growth. In the Karpas-299 transplantation tumor mouse model, AP26113 (<50 mg/kg) inhibited p-ALK. In the Karpas-299 transplantation tumor mouse model and the H3122 transplantation tumor mouse model, AP26113 (<50 mg/kg) inhibited tumor growth.

Leflunomide inhibited growth in SU-DHL-1 (GI50=9 nM), H3122 (GI50=4 nM) and Ba/F3-EML4-ALK v1 (1 gI50=3 nM) cell lines. In NSCLC cell lines expressing EGFR-DEL (HCC827) (IC50=62 nM), AP26113 acted to inhibit EGFR phosphorylation and inhibited cell growth.

Three-day cell viability assays are carried out by plating 2,000, 1,500 and 2,000 cells per well of Ba/F3, PC9 or MGH121, respectively, into black transparent-bottom 96-well plates. On the same day for Ba/F3 cells and the following day for PC9 and MGH121 cells, the cells are treated with each TKI across a 10-dose range from 0.3 nM to 10 μM. After 72 h of drug treatment, cell viability is measured using the CellTiter-Glo assay. (Only for Reference)