CH5424802 (Synonyms: Alectinib, RO5424802)

CH5424802 is a potent and selective ALK inhibitor.

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that is constitutively activated in certain cancers. .

In vitro: In cell free assays the IC50 of CH5424802 for enzyme activity of ALK was 1.9 nM; the dissociation constant (KD) value for ALK in an ATP-competitive manner was 2.4 nM. The inhibitory activity for two hot spot-activating mutations (F1174L and R1275Q) in neuroblastoma was comparable to that for wildtype ALK [1].

In vivo: In the NCI-H2228 model, oral administration of CH5424802 resulted in dose-dependent tumor growth inhibition (ED50 = 0.46 mg/kg) and tumor regression. Moreover, treatment of 20 mg/kg CH5424802 showed rapid tumor regression and tumor regrowth did not occur throughout the 4-week drug-free period [2].

Clinical trial: No clinical data are available currently.

Reference:
[1] Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, Oikawa N, Tsukuda T, Ishii N, Aoki Y.  CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.