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 (μgh/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. |
![Pyrazolo[3,4-b]indole-5-carboxylic acid, 2,8-dihydro-2-methyl-8-[4-(trifluoromethyl)phenyl]- Structure](https://www.chemicalbook.com/CAS/20210305/GIF/2738542-58-8.gif)
