INCB13739 is an orally active, potent, selective, and tissue-specific inhibitor of 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), with IC50 values of 3.2 nM (11β-HSD1 enzymatic) and 1.1 nM (11β-HSD1 PBMC). It is used in research for type 2 diabetes mellitus (T2DM) and obesity [1].

INCB13739 is over 1000-fold selective for 11β-HSD2, mineralocorticoid receptor (MR), and glucocorticoid receptor (GR) [1].

INCB13739, administered orally, has shown effective distribution in adipose tissue, inhibiting 11β-HSD1 activity by over 90% for at least 24 hours after dosing [1]. This compound displays satisfactory oral bioavailability in both rats and cynomolgus monkeys when administered once at doses of 3 mg/kg intravenously (IV) or 10 mg/kg orally (PO) [1]. The pharmacokinetic analysis in rats revealed the following parameters: with an IV dosage of 3 mg/kg, the maximum concentration (Cmax) was 6.46 ± 2.41 μM, the area under the curve (AUC) from 0-24 hours was 11.2 ± 3.27 ng/mL·h, the half-life (t1/2) was 1.4 ± 0.2 hours, the clearance rate (CL) was 1.0 ± 0.2 (L/h)/kg, the steady-state volume of distribution (Vdss) was 1.6 ± 0.5 L/kg, and the bioavailability (F%) was 51 ± 15%. These results, relevant to both rats and cynomolgus monkeys, underscore INCB13739's pharmacokinetics and support its potential for effective oral administration [1].