MSC-4106

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MSC-4106 是一种具有口服活性的 YAP/TAZ-TEAD 抑制剂。 MSC-4106 阻断 TEAD1 和 TEAD3 的 auto-palmitoylation，对 NCI-H226 异种移植瘤模型具有抑制作用。

MSC-4106 is an orally active and potent inhibitor of YAP/TAZ-TEAD. MSC-4106 inhibits TEAD1 or TEAD3 auto-palmitoylation and shows inhibitory effect on NCI-H226 tumor xenograft model.

MSC-4106 (10 μM, 24 h) inhibited SK-HEP-1 reporter and NCI-266 cell viability with IC50 values of 4 nM and 14 nM, respectively.MSC-4106 (10 μM, 6 h) crystallizes in the P-site of TEAD1, and against TEAD1 or TEAD3 palmitoylation in TEAD-Overexpressing HEK293 Cells by 97.3% and 75.9%, respectively.MSC-4106 (10 μM, 4 d) targets TEAD indicated by a reduction in viability of NCI-H226 cells.Cell Viability Assay Cell Line:NCI-H226 (YAP dependent); SW620 YAP/TAZ KO (Yap-independent) cells Concentration:0, 3, 6, 9, 12, 15, 18, 21, 24, 26, 30 μM Incubation Time:96 hours Result:Showed inhibitory effect to NCI-H226 and general cytotoxic to SW620 (IC50 >30 μM).Immunofluorescence Cell Line:SK-HEP-1Concentration:0, 3, 6, 9, 12, 15, 18, 21, 24, 26, 30 μM Incubation Time:24 hours Result:Inhibited YAP-TEAD interation.

MSC-4106 (100 mg/kg/d; p.o.; 7 d) displays anti-tumor effect with controlled tumor volume and good tolerability with stable body weight in mice.MSC-4106 (1, 5, 100 mg/kg/d; p.o.; 0-72 h) down-regulates Cyr61 (cysteine-rich angiogenic inducer 61) expression, the TEAD-regulated target gene, in tumor lysates at all time points at 100 mg/kg and 24 h at 5 mg/kg.Note: PO studies were performed at 10 mg/kg; MSC-4106 was formulated in 20% Kleptose in 50 mM PBS at pH 7.4.Animal Model:NCI-H226 xenograft model in H2d Rag2 female mice (9-week-old)Dosage:5, 100 mg/kg Administration:Oral gavage; once daily; 32 days Result:Resulted tumor growth controlled with 5 mg/kg while regressed with 100 mg/kg dosing after 32 treatment days.

——

Others

Other Targets

YAP

——

——

2738542-58-8

359.3

C18H12F3N3O2

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 250 mg/mL (695.80 mM; 超声助溶 )

Cn1cc2c3cc(ccc3n(-c3ccc(cc3)C(F)(F)F)c2n1)C(O)=O

——

(-20℃)

With Ice Pack

≥ 2 years