Discovery and efficacy study of an ALK inhibitor AMX6001 in anaplastic large cell lymphoma Karpas299 mice models

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 9 ( AMX6001 ) showed better in vitro activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. In vivo efficacy of compound 9 was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound 9 (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models. • Compound 9 is a potent orally bioavailable ALK inhibitor with an IC 50 (NPM-ALK) = 0.17 nM. • Compound 9 showed very good anti-proliferative activity against Karpas 299 (IC 50 = 7.64 nM) and SU-DHL-1 (IC 50 = 7.01 nM) cell lines. • Compound 9 (25 mg/kg) induced tumor suppression TGI upto 95.8 % in Karpas 299 ALCL models.