X-376 |cas 1365267-27-1|DC Chemicals

Cas No.:	1365267-27-1
Chemical Name:	X-376
Synonyms:	X-396;6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyridazine-3-carboxamide;X 396;X-376;6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-3-pyridazinecarboxamide;Ensartinib;7DR7JMB8BH;(R)-6-Amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-N-(4-(4-methylpiperazine-1-carbonyl)phenyl)pyridazine-3-carboxamide;GTPL8959;BCP07190;BDBM50432894;NSC8009;NSC800968;s6505;DB13104;Example 18 [WO2012048259];3-Pyridazinecarboxamide, 6-amino-5-((1R)-1-(2,6-dic
SMILES:	ClC1=C(C([H])=C([H])C(=C1[C@@]([H])(C([H])([H])[H])OC1C(N([H])[H])=NN=C(C=1[H])C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])C(N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])=O)=O)Cl)F
Formula:	C₂₅H₂₅Cl₂FN₆O₃
M.Wt:	547.4088
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	X-376 is a potent and dual ALK/MET inhibitor with IC50s of 0.61 nM and 0.69 nM, 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 μM×hr and a Cmax of 5.04 μM[1].
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[1].
Animal Administration:	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 50 mg/kg X-376 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.

Cat. No.	Product name	Field of application
DC10463	Repotrectinib(TPX-005)	Repotrectinib(TPX-005) is a multi-target macrocycle inhibitor of anaplastic lymphoma kinase (ALK), c-ros proto-oncogene 1 receptor tyrosine kinase (ROS1), and neurotrophic tyrosine kinase receptor (TRK)
DC2047	Crizotinib (PF-2341066)	PF-2341066 (Crizotinib) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nnM, respectivley.
DC7924	PF06463922(Lorlatinib)	PF06463922 is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.
DC7303	NVP-TAE684	NVP-TAE684(TAE684) is a highly potent and selective small-molecule ALK inhibitor, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM.
DC8034	LDN193189 free base	LDN193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively.
DC8127	KRCA-0008	KRCA-0008 is a potent Ack1 and anaplastic lymphoma kinase (ALK) dual inhibitor (IC50 values are 4 and 12 nM respectively).
DC10547	X-376	X-376 is a highly selective and potent inhibitor of ALK (anaplastic lymphoma kinase) tyrosine kinase, demonstrating strong activity with an IC50 of 0.61 nM. While it primarily targets ALK, it also exhibits inhibitory effects on MET kinase, though with slightly reduced potency (IC50 = 0.69 nM). Due to its robust kinase-blocking properties, X-376 shows significant anti-tumor efficacy, making it a promising candidate for cancer research and therapeutic development.
DC8728	CH5424802(Alectinib HCl)	CH5424802(AF 802; Alectinib) is a potent ALK inhibitor with IC50 of 1.9 nM, sensitive to L1196M mutation.
DC8138	CEP-28122	CEP-28122 is a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers.
DC7359	Asp-3026	ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM.