GNF4877

生物活性靶点体外研究体内研究 GNF4877 试剂级价格

GNF4877

CAS号:2041073-22-5
英文名:GNF4877
中文名:GNF4877
CBNumber:CB55540441
分子式:C25H27FN6O4
分子量:494.52
MOL File:2041073-22-5.mol

GNF4877化学性质

沸点 :669.7±55.0 °C(Predicted)
密度 :1.367±0.06 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMSO: 4.17 mg/mL (8.43 mM and warming)
酸度系数(pKa) :2.82±0.70(Predicted)

GNF4877性质、用途与生产工艺

生物活性 GNF4877是 DYRK1A 和 GSK3β 的有效抑制剂，IC50 值分别为 6 nM 和 16 nM，可导致 NFATc 核输出受阻并增加 β 细胞增殖 (对小鼠 β (R7T1) 细胞的 EC50 值为 0.66 μM)。
靶点

GSK3β

16 nM (IC ₅₀ )

DYRK1A

6 nM (IC ₅₀ )
体外研究

High glucose concentrations and glucokinase activators (GKAs) increase Ca ²⁺ signalling in β-cells, and increase intracellular Ca ²⁺ leads to activation of calcineurin and nuclear translocation of NFATc proteins. Indeed, concentrations of GNF4877 ((0.1 μM, 0.3 μM) well below the EC ₅₀ for β-cell proliferation are able to induce proliferation in the presence of high glucose or pharmacological activators of glucokinase. Finally, increasing intracellular Ca ²⁺ with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca ²⁺ channel activator) show additive activity with GNF4877.

体内研究

GNF4877 (50 mg/kg; oral gavage; twice a day; for 15 days; double transgenic RIP-DTA male mice) treatment induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control.

Animal Model:	Double transgenic RIP-DTA male mice (Tg (Ins 2-rtTA) 2 Efr Tg (teto-DTA) 1 Gfi/J) with Doxycycline (28.8±2.4 g; 82±2 days)
Dosage:	50 mg/kg
Administration:	Oral gavage; twice a day; for 15 days
Result:	Induced β-cell proliferation, increased β-cell mass and insulin content, and improved glycaemic control.