INCB13739

• CAT Number: I043321
• CAS Number: 869974-19-6
• Molecular Formula: C28H25N3O4
• Molecular Weight: 467.52
• Purity: ≥95%
• Synonyms: N-methyl-5-[4-[1-[(1R)-3-oxospiro[2-benzofuran-1,3′-pyrrolidine]-1′-carbonyl]cyclopropyl]phenyl]pyridine-2-carboxamide
• InChI: InChI=1S/C28H25N3O4/c1-29-24(32)23-11-8-19(16-30-23)18-6-9-20(10-7-18)27(12-13-27)26(34)31-15-14-28(17-31)22-5-3-2-4-21(22)25(33)35-28/h2-11,16H,12-15,17H2,1H3,(H,29,32)/t28-/m0/s1
• InChIKey: BDQCDIWFPIDPQU-NDEPHWFRSA-N
• SMILES: CNC(=O)C1=NC=C(C=C1)C2=CC=C(C=C2)C3(CC3)C(=O)N4CCC5(C4)C6=CC=CC=C6C(=O)O5

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].
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

Reference

[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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