Alectinib(Alecinix) is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, Alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions,amplifications, or activating mutations.The major active metabolite of Alectinib, M4, showed similar in vitro potency and activity.
Alectinib and M4 demonstrated in vitro and in vivo activity against multiple mutant forms of the ALK enzyme, including some mutations identified in NSCLC tumors in patients who have progressed on Crizotinib.
In mouse models implanted with tumors carrying ALK fusions, administration of Alectinib resulted in antitumor activity and prolonged survival, including in mouse models implanted intracranially with ALK-driven tumor cell lines.
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