GNF2133 hydrochloride 是一种有效的、选择性的、具有口服活性的DYRK1A抑制剂，对 DYRK1A 和 GSK3β 的IC50分别为 0.0062、>50 μM。GNF2133 hydrochloride 对大鼠和人原代 β 细胞具有良好的增殖能力和功效。GNF2133 hydrochloride 显著提高葡萄糖处理能力并增加胰岛素分泌。GNF2133 hydrochloride 具有研究1型糖尿病的潜力。

GNF2133 hydrochloride is a potent, selective and orally active DYRK1A inhibitor with IC 50 s of 0.0062, >50 μM for DYRK1A and GSK3β, respectively. GNF2133 hydrochloride shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 hydrochloride significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 hydrochloride has the potential for the research of type 1 diabetes [1].

GNF2133 hydrochloride (30 mg/kg; p.o.) shows good oral absorption with oral bioavailability of 22.3% [1]. GNF2133 hydrochloride (30 mg/kg; p.o.; once a day for 5 days) shows the ability to proliferate β-cells in vivo [1]. GNF2133 hydrochloride (3, 10, 30 mg/kg) significantly improves glucose disposal capacity and increased insulin secretion in RIP-DTA mice [1]. Pharmacokinetic Parameters of GNF2133 hydrochloride in CD-1 mice [1]. plasma (iv) plasma (po) pancreas (po) CL (mL/min/kg) 23.5 V ss (L/kg) 11 AUC (h·nM) 3268 10974 144420 C max (nM) 1977 1675 13319 t max<(h) 0.03 3.0 3.0 C last (nM) 36.6 19 1324 t 1/2<(h) 6.6 3.4 6.6 F (%) 22.3 CD-1 mice; 30 mg/kg; p.o.sup>[1]. Animal Model: CD-1 mice [1] Dosage: 30 mg/kg Administration: P.o. Result: Showed good oral absorption and moderate plasma exposure with oral bioavailability of 22.3%. Animal Model: Wistar Han rat [1] Dosage: 30 mg/kg (0.5% methylcellulose + Tween-80) Administration: P.o.; once a day for 5 days Result: Increased cyclin D1 levels and overall cell density, and increased in cell proliferation marker Ki67 and insulin. Animal Model: Diphtheria toxin A (RIP-DTA) mice [1] Dosage: 3, 10, 30 mg/kg (20 mg/kg doxycycline (Dox) for 5 days) Administration: P.o., once a day for 35 days Result: Significantly improves glucose disposal capacity and increased insulin secretion.

2561414-57-9

C24H31ClN6O2

470.99

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years