| Description |
INCB13739 is an orally active, potent, selective and tissue-specific11β-HSD1 (11β-hydroxysteroid dehydrogenase 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].
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| Related Catalog |
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| Target |
IC50: 3.2 nM (11β-HSD1 enzymatic), 1.1 nM (11β-HSD1 PBMC)[1]
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| In Vitro |
INCB13739 is >1000-fold selective towards 11β-HSD2, mineralocorticoid receptor (MR), and glucocorticoid receptor (GR)[1].
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| In Vivo |
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%).
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| References |
[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.
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