BMS-986339 (compound 32, p.o., 10 mg/kg, once daily for 9 days) induces Fgf15 production, and shows antifibrotic efficacy in mouse bile duct ligation (BDL) model[1].
BMS-986339 (p.o. or i.v., 5 mg/kg or 1 mg/kg) exhibits low clearance and a long elimination half-life in mice and rats[1].
| Animal Model: | Mouse bile duct ligation (BDL) model[1] |
| Dosage: | 0.3, 1, 3, and 10 mg/kg, once daily for 9 days. |
| Administration: | Oral administration |
| Result: | Induced Fgf15 and SHP (small heterodimer partner) gene expression to a similar extent in the ileum.
Decreased the ratio of hydroxyproline to the total protein content, and decreased the collagen levels.
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| Animal Model: | Male C57BL6 mice, male Sprague-Dawley rat (pharmacokinetic assay)[1] |
| Dosage: | 5 mg/kg or 1 mg/kg |
| Administration: | Oral administration, intravenous injection |
| Result: | Pharmacokinetic profile of BMS-986339 (compound 32).
| parameter | male C57BL6 mice | male Sprague-Dawley rat | | dose (mg/kg) i.v. | 1 | 1 | | dose (mg/kg) p.o. | 5 | 2 | | Vss (L/kg) i.v. | 2.2 | 5.2 | | AUCtotal (μM?h) i.v. | 16.4 | 6.6 | | AUCtotal (μM?h) p.o. | 56.6 | 5.8 | | t1/2 h (i.v.) | 16 | 18 | | Fp.o. | 69 | 40 |
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