| Identification | Back Directory | [Name]
Pyrazolo[3,4-b]indole-5-carboxylic acid, 2,8-dihydro-2-methyl-8-[4-(trifluoromethyl)phenyl]- | [CAS]
2738542-58-8 | [Synonyms]
MSC4106
MSC-4106
MCS-4106
Pyrazolo[3,4-b]indole-5-carboxylic acid, 2,8-dihydro-2-methyl-8-[4-(trifluoromethyl)phenyl]- | [Molecular Formula]
C18H12F3N3O2 | [MOL File]
2738542-58-8.mol | [Molecular Weight]
359.3 |
| Chemical Properties | Back Directory | [Boiling point ]
479.7±45.0 °C(Predicted) | [density ]
1.48±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C, away from moisture | [solubility ]
DMSO : 250 mg/mL (695.80 mM; Need ultrasonic) | [form ]
Solid | [pka]
4.17±0.30(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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.
| 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. |
| [IC 50]
YAP/TAZ-TEAD | [References]
[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. DOI:10.1021/acs.jmedchem.2c00403 |
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