X-396 hydrochloride

Modify Date: 2024-01-09 10:32:25

X-396 hydrochloride structure	Common Name	X-396 hydrochloride
	CAS Number	2137030-98-7	Molecular Weight	634.36
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₂₆H₂₉Cl₄FN₆O₃	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of X-396 hydrochloride

Ensartinib hydrochloride (X-396 hydrochloride) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively.

Name	X-396 hydrochloride

Description	Ensartinib hydrochloride (X-396 hydrochloride) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively.
Related Catalog	Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ALK Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Met/HGFR Research Areas >> Cancer
Target	IC50: <0.4 nM (ALK), 0.74 nM (MET)[1]
In Vitro	Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively. Ensartinib is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC50: 15 nM). Ensartinib 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)[1].
In Vivo	Ensartinib (X-396) shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib at 25 mg/kg bid. Ensartinib significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib 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. At NST levels, Ensartinib achieves an AUC of 66 μM×hr and a Cmax of 7.19 μM[1].
Cell Assay	For viability experiments, cells are seeded in 96-well plates at 25%-33% confluency and exposed to drugs. The human lung adenocarcinoma cell lines H3122 and H2228 are treated with Ensartinib (10, 30, 100, 300 and 1000 nM). SUDHL-1 lymphoma cells are treated with Ensartinib (5, 10, 30, 100 and 300 nM). SY5Y neuroblastoma cells are treated with Ensartinib (30, 100, 300 and 1000 nM). At 72 hours post Ensartinib addition, Cell Titer Blue Reagent is added and fluorescence is measured on a Spectramax spectrophotometer. All experimental points are set up in hextuplicate replicates and are performed at least two independent times. IC50s are calculated using GraphPad Prism version 5 for Windows. The curves are fit using a nonlinear regression model with a log (inhibitor) vs. response formula[1].
Animal Admin	Mice[1] Nude mice (nu/nu) are injected with H3122 cells. Once tumors reach an average volume of 450 mm3, a total of 27 athymic mice harboring H3122 tumors are randomized and dosed via oral gavage with 25 mg/kg Ensartinib or the control vehicle. Two, five, and fifteen hours after the single treatment (3 tumors/timepoint/group), mice are sacrificed and serum is collected for assessment of drug concentration using an LC-MS based bioanalytical method[1].
References	[1]. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31.

Molecular Formula	C₂₆H₂₉Cl₄FN₆O₃
Molecular Weight	634.36