IHMT-MST1-58

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

IHMT-MST1-58 是一种有效的、选择性的 STE20-like protein 1 kinase (MST1) 抑制剂，具有口服活性，IC50 值为 23 nM。IHMT-MST1-58 可用于 1 型或 2 型糖尿病的研究。

IHMT-MST1-58 is a potent, selective mammalian and orally active STE20-like protein 1 kinase (MST1) inhibitor with IC50 value of 23 nM. IHMT-MST1-58 can be used for the research of Type 1/2 diabetes.

IHMT-MST1-58 (compound 19) shows good activity against MST1 with an IC50 value of 23 nM.IHMT-MST1-58 (1 μM) displays strong inhibitory activity against MST1 (IC50 = 23 nM), weak activity against MST2 (IC50 = 652 nM), but no activity against NEK3 even at 10 μM (IC50 > 10 μM) .IHMT-MST1-58 (1 μM) shows strong binding affinity to MST1 and weak binding affinity to MST2 with Kd values of 240 nM and 2.7 μM.IHMT-MST1-58 (0.1-10 μM; 1-2 h) inhibits the phosphorylation of MST1 in vitro.IHMT-MST1-58 (0.03, 0.1 and 0.3 μM; 48 h) exhibits a significant protective effect of β cells from the damage caused by inflammatory cytokines.Western Blot Analysis Cell Line:HepG2 liver cells, RAW264.7, RPE1 and HL7702 cells; INS-1 and RIN-m5F cell lines Concentration:0-10 μM Incubation Time:2 h (HepG2 liver cells, RAW264.7, RPE1, and HL7702 cells) Result:Inhibited the H2O2-stimulated MOB1 phosphorylation and MST1/2 autophosphorylation in a dose-dependent manner in all four cell lines.Inhibited the phosphorylation of LATS1 (T1079) and YAP (S127) in HepG2 cells.Showed strong inhibition of MST1 phosphorylation and its downstream MOB1 autophosphorylation in a dose-dependent manner in both cell lines.

IHMT-MST1-58 (compound 19) (p.o, 50 mg/kg/day, QD) combination with metformin led to the decline of fasting blood glucose, show protective effect of β cells and decrease the hemoglobin A1c level in the STZ-induced T1D/T2D mouse models. Pharmacokinetic Parameters of IHMT-MST1-58 in different species (i.v. or p.o; 1 mg/kg, 5 mg/kg and 10 mg/kg).Animal Model:T1D mouse models and T2D mouse models Dosage:50 mg/kg Administration:p.o, 50 mg/kg/day, QD Result:Decreased the FBG level, improved the food intake and water consumption, had lowHbA1c and a goodantidiabetic effect, improved the histological structure of the islet. Animal Model:mice, Sprague Dawley rats, and beagle dogs Dosage:1 mg/kg, 5 mg/kg and 10 mg/kg Administration:intravenous injection and oral administration Result:Displayed acceptable pharmacokinetic properties in different species.

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Others

Other Targets

Hippo pathway

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2414484-25-4

438.5

C21H22N6O3S

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 100 mg/mL (228.05 mM; 超声助溶 (<80°C)

CN1C=2C(N(C)C(=O)C1C3=C(C)C=CC=C3)=CN=C(NC4=CC=C(S(N)(=O)=O)C=C4)N2

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(-20℃)

With Ice Pack

≥ 2 years