IC50: 3.2 nM (11β-HSD1 enzymatic), 1.1 nM (11β-HSD1 PBMC)[1]
INCB13739 is an orally active, potent, selective and tissue-specific11β-HSD1 (11β-droxysteroid dedrogenase 1) inhibitor, with IC50 values of 3.2 nM (11β-HSD1 enzymatic) and 1.1 nM (11β-HSD1 PBMC), respectively. INCB13739 can be used for type 2 diabetes mellitus (T2DM) and obesity research[1].
INCB13739 is >1000-fold selective towards 11β-HSD2, mineralocorticoid receptor (MR), and glucocorticoid receptor (GR)[1].
INCB13739 (Orally) is effectively distributed in the adipose tissue and is inhibiting 11β-HSD1 activity > 90% for at least 24 h post-dose[1].
INCB13739 (3 mg/kg, IV; 10 mg/kg, PO; once) displays decent oral bioavailability in both rats and cynomolgus monkeys[1].
Pharmacokinetic Parameters of INCB13739 in rats[1].
| IV (3 mg/kg) | PO (10 mg/kg) | |
| Cmax (µM) | 6.46 ± 2.41 | |
| AUC0-24 (ng/mL∗h) | 11.2 ± 3.27 | |
| t1/2 (h) | 1.4 ± 0.2 | 1.2 ± 0.3 |
| CL ((L/h)/kg) | 1.0 ± 0.2 | |
| Vdss (L/kg) | 1.6 ± 0.5 | |
| F (%) | 51 ± 15 |
| Animal Model: | Rats, cynomolgus monkeys[1] |
| Dosage: | 3 mg/kg (IV), 10 mg/kg (PO) |
| Administration: | IV and PO, once (Pharmacokinetic Analysis) |
| Result: | Displayed decent oral bioavailability in both rats (F%=51 ± 15%) and cynomolgus monkeys (F%=43%). |
[1]. Marando C, et al. Discovery of 1'-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3'-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach. Bioorg Med Chem Lett. 2022 Aug 1;69:128782.