MSC-4106

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

MSC-4106 

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

MSC-4106 Chemical Structure

CAS No. : 2738542-58-8

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生物活性

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[1].

体外研究
(In Vitro)

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[1].
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[1].
MSC-4106 (10 μM, 4 d) targets TEAD indicated by a reduction in viability of NCI-H226 cells[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

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[1]

Cell Line: SK-HEP-1
Concentration: 0, 3, 6, 9, 12, 15, 18, 21, 24, 26, 30 μM
Incubation Time: 24 hours
Result: Inhibited YAP-TEAD interation.

体内研究
(In Vivo)

MSC-4106 (P.O.; 100 mg/kg once daily; 7 days) displays anti-tumor effect with controlled tumor volume and good tolerability with stable body weight in mice[1].
MSC-4106 (P.O.; 1, 5, 100 mg/kg once daily; 6, 24, 30, 48, and 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[1].
Pharmacokinetics (PK) profile in different species[1]

Parameter Mouse Rat Dog
Cl (l/h/kg) 0.2 0.7 0.05
PO t1/2 (h) 45 40 3.6
PO AUC (μg•h/mL) 45 10 33
Vss (L/kg) 2 5 0.3
F (%) >90 80 18

Note: PO studies were performed at 10 mg/kg; MSC-4106 was formulated in 20% Kleptose in 50 mM PBS at pH 7.4.

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: NCI-H226 xenograft model in H2d Rag2 female mice (9-week-old)[1]
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.

分子量

359.30

Formula

C18H12F3N3O2
CAS 号

2738542-58-8
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Timo Heinrich, et al. Optimization of TEAD P-site binding fragment hit into in vivo active lead MSC-4106. J. Med. Chem. 2022, 65, 13, 9206–9229.

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