FOXO1-IN-3

• CAT Number: I040925
• CAS Number: 2451093-95-9
• Molecular Formula: C22H23N7O
• Molecular Weight: 401.46
• Purity: ≥95%
• Synonyms: N-[5-(1H-benzimidazol-2-yl)-1H-pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
• InChI: InChI=1S/C22H23N7O/c1-28-10-12-29(13-11-28)16-8-6-15(7-9-16)22(30)25-20-14-19(26-27-20)21-23-17-4-2-3-5-18(17)24-21/h2-9,14H,10-13H2,1H3,(H,23,24)(H2,25,26,27,30)
• InChIKey: OYUAMDGBOAEJOY-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)C4=NC5=CC=CC=C5N4

FOXO1-IN-3 is a highly-selective and orally active FOXO1 inhibitor. FOXO1-IN-3 reduces hepatic glucose production in mice. FOXO1-IN-3 improves insulin sensitivity and glucose control in db/db mice without causing weight gain[1].
FOXO1-IN-3 (Compound 10) (10 μM, 6 h) suppresses cAMP/Dexamethasone (HY-14648) induced G6pc and Pck1 mRNA expression in primary hepatocytes isolated from normal mice[1].
FOXO1-IN-3 (Compound 10) (16 mg/kg, p.o., twice daily, for 10 days) reduces blood glucose in db/db mice[1].
FOXO1-IN-3 (16 mg/kg, p.o., twice daily, for 7 days) and FGF21 (0.45 mg/kg) has synergistic glucose-lowering effects in Streptozotocin (HY-13753) induced β-cell-ablated diabetic mice[1].
FOXO1-IN-3 (1 mg/kg for i.v., 10 mg/kg for p.o.) shows significant plasma exposure and oral bioavailability despite relatively short half-life in mice[1].
PK properties of FOXO1-IN-3 (compound 10)

Dose (mg/kg)
parameters
value

i.v. (1 mg/kg)
T1/2
1.23 h

AUCinf
1.86 μM·h

CL
22.7 mL/kg·min

p.o. (10 mg/kg)
Tmax
0.67 h

AUCinf
4.66 μM·h

F%
25.5%

Reference

[1]. Lee YK, et al. FOXO1 inhibition synergizes with FGF21 to normalize glucose control in diabetic mice. Mol Metab. 2021 Jul;49:101187.
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