MSC-4106

• CAT Number: I043431
• CAS Number: 2738542-58-8
• Molecular Formula: C18H12F3N3O2
• Molecular Weight: 359.30
• Purity: ≥95%
• Synonyms: 2-methyl-4-[4-(trifluoromethyl)phenyl]pyrazolo[3,4-b]indole-7-carboxylic acid
• InChI: InChI=1S/C18H12F3N3O2/c1-23-9-14-13-8-10(17(25)26)2-7-15(13)24(16(14)22-23)12-5-3-11(4-6-12)18(19,20)21/h2-9H,1H3,(H,25,26)
• InChIKey: HUSMWXZHQVTDRU-UHFFFAOYSA-N
• SMILES: CN1C=C2C3=C(C=CC(=C3)C(=O)O)N(C2=N1)C4=CC=C(C=C4)C(F)(F)F

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].
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].
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[1].
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[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.

Reference

[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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