| Identification | Back Directory | [Name]
INCB13739 | [CAS]
869974-19-6 | [Synonyms]
INCB13739
2-Pyridinecarboxamide, N-methyl-5-[4-[1-[[(1R)-3-oxospiro[isobenzofuran-1(3H),3'-pyrrolidin]-1'-yl]carbonyl]cyclopropyl]phenyl]- | [Molecular Formula]
C28H25N3O4 | [MOL File]
869974-19-6.mol | [Molecular Weight]
467.52 |
| Chemical Properties | Back Directory | [Boiling point ]
777.2±60.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
12.97±0.46(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
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]. | [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%). |
| [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. DOI:10.1016/j.bmcl.2022.128782 |
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