Ensartinib

Ensartinib, also known as X-396, is an orally available small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with potential antineoplastic activity. Upon oral administration, X-396 binds to and inhibits ALK kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. (In Vitro) :The ability of X-376 to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. X-376 is potent in H3122 lung cancer cells harboring EML4-ALK E13; A20 (IC50: 77 nM) . X-376 is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC50: 57 nM) . Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 32 nM) . X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC50s of 142 nM, 150 nM, 15.137 μM and 3.062 μM, respectively. (In Vivo) :The effects of X-376 in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that X-376 shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with X-376 at 50 mg/kg bid. X-376 significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, X-376 appears well-tolerated in vivo. Mouse weight is unaffected by X-376 treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of X-376, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of X-376 at 25, 50, 100 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 50 mg/kg for X-376. At NST levels, X-376 achieves an AUC of 41 μMxhr and a Cmax of 5.04 μM.

1365267-27-1

X396 | X-396 | X 396 | Ensartinib

>98% (HPLC)

DMSO : ≥ 37 mg/mL 67.59 mM

C1 (cc (c (nn1) N) O[C@H] (C) c1c (c (ccc1Cl) F) Cl) C (=O) Nc1ccc (cc1) C (=O) N1CCN (CC1) C

C25H25Cl2FN5O3

547.41

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.