GNF2133

• CAT Number: I045212
• CAS Number: 2561414-56-8
• Molecular Formula: C24H30N6O2
• Molecular Weight: 434.53
• Purity: ≥95%
• Synonyms: 4-ethyl-N-[4-[1-(oxan-4-yl)pyrrolo[2,3-c]pyridin-3-yl]pyridin-2-yl]piperazine-1-carboxamide
• InChI: InChI=1S/C24H30N6O2/c1-2-28-9-11-29(12-10-28)24(31)27-23-15-18(3-8-26-23)21-17-30(19-5-13-32-14-6-19)22-16-25-7-4-20(21)22/h3-4,7-8,15-17,19H,2,5-6,9-14H2,1H3,(H,26,27,31)
• InChIKey: SAZIAQSVBIWIDU-UHFFFAOYSA-N
• SMILES: CCN1CCN(CC1)C(=O)NC2=NC=CC(=C2)C3=CN(C4=C3C=CN=C4)C5CCOCC5

GNF2133 is a potent, selective and orally active DYRK1A inhibitor with IC50s of 0.0062, >50 µM for DYRK1A and GSK3β, respectively. GNF2133 shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 has the potential for the research of type 1 diabetes[1].
GNF2133 (30 mg/kg; p.o.) shows good oral absorption with oral bioavailability of 22.3%[1].
GNF2133 (30 mg/kg; p.o.; once a day for 5 days) shows the ability to proliferate β-cells in vivo[1].
GNF2133 (3, 10, 30 mg/kg) significantly improves glucose disposal capacity and increased insulin secretion in RIP-DTA mice[1].
Pharmacokinetic Parameters of GNF2133 in CD-1 mice[1].

plasma (iv)
plasma (po)
pancreas (po)

CL (mL/min/kg)
23.5
/
/

Vss (L/kg)
11
/
/

AUC (h·nM)
3268
10974
144420

Cmax(nM)
1977
1675
13319

tmax<(h) 0.03 3.0 3.0 Clast(nM) 36.6 19 1324 t1/2<(h) 6.6 3.4 6.6 F (%) / 22.3 / CD-1 mice; 30 mg/kg; p.o.[1].

Reference

[1]. Liu YA, et al. Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133. J Med Chem. 2020 Mar 26;63(6):2958-2973.
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