Ensartinib hydrochloride

Research use only, not for human use.

Ensartinib dihydrochloride is a potent new-generation ALK inhibitor with high activity against CNS metastases and a broad range of known crizotinib-resistant ALK mutations.

Ensartinib dihydrochloride is a potent new-generation ALK inhibitor with high activity against CNS metastases and a broad range of known crizotinib-resistant ALK mutations. It potently inhibits both wild-type ALK and ALK variants (C1156Y, F1174, G1202R, L1196M, S1206R, and T1151 mutants) with in vitro IC50s of <4 nM.(In Vitro):Ensartinib potently inhibits both wild-type ALK and all evaluated ALK variants (C1156Y, F1174, G1202R, L1196M, S1206R, and T1151 mutants) with in vitro IC50s of <4 nM. Besides ALK, ensartinib also potently inhibits GOPC-ROS1, TPM3-TRKA, and TRKC with an IC50 of <1 nM, and inhibits EphA1, EphA2, EphB1 and c-MET with an IC50 of 1-10 nM.

Ensartinib (X-396) dihydrochloride is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively. Ensartinib dihydrochloride is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC50: 15 nM). Ensartinib dihydrochloride is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC50: 45 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 9 nM).

Ensartinib (X-396) dihydrochloride shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib dihydrochloride at 25 mg/kg bid. Ensartinib dihydrochloride significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib dihydrochloride appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib dihydrochloride treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib dihydrochloride, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib dihydrochloride at 20, 40, 80 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 80 mg/kg for Ensartinib dihydrochloride. At NST levels, Ensartinib dihydrochloride achieves an AUC of 66 μM×hr and a Cmax of 7.19 μM.

Ensartinib dihydrochloride | X-396 dihydrochloride

Others

Other Targets

mitochondrial cytochrome bc1

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2137030-98-7

634.36

C26H29Cl4FN6O3

>98% (HPLC)

In Vitro:?DMSO : 35.71 mg/mL (56.29 mM)

Cl.Cl.CC(Oc1cc(nnc1N)C(=O)Nc1ccc(cc1)C(=O)N1CC(C)NC(C)C1)c1c(Cl)ccc(F)c1Cl

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(-20℃)

With Ice Pack

≥ 2 years