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。
| 生物活性 | IHMT-MST1-58 is a potent, selective mammalian and orally activeSTE20-like protein 1 kinase (MST1)inhibitor withIC50value of 23 nM. IHMT-MST1-58 can be used for the research of Type 1/2 diabetes[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | IHMT-MST1-58 (compound 19) shows good activity against MST1 with an IC50value of 23 nM[1].
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)[1].
IHMT-MST1-58 (1 μM) shows strong binding affinity to MST1 and weak binding affinity to MST2 with Kdvalues of 240 nM and 2.7 μM[1].
IHMT-MST1-58 (0.1-10 μM; 1-2 h) inhibits the phosphorylation of MST1 in vitro[1].
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[1].
Western Blot Analysis[1] | 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. |
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体内研究
(In Vivo) | 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[1].
Pharmacokinetic Parameters of IHMT-MST1-58 in different species (i.v. or p.o; 1 mg/kg, 5 mg/kg and 10 mg/kg)[1].
| mice | rats | beagle dogs | | parameter | i.v.(1 mg/kg) | p.o.(10 mg/kg) | i.v.(1 mg/kg) | p.o.(10 mg/kg) | i.v.(1 mg/kg) | p.o.(10 mg/kg) | | AUC0-t(ng/mL*h) | 501.1 | 5583 | 2553±155.1 | 4858±2648 | 764.5±82.9 | 4939±1067 | | t1/2(h) | 1.7 | 1.81 | 3.51±0.34 | 3.03±0.2 | 6.47±0.71 | 5.79±1.09 | | Cmax/F (ng/mL) | 1240 | 1922 | 944.0±219.1 | 1717±276 | 466.7±45.2 | 1113±417 | | F(%) | - | 110.8 | - | 73.3±40.1 | - | 106.5±20.9 |
| Animal Model: | mice[1] | | Dosage: | 50 mg/kg | | Administration: | oral, single | | Result: | | parameter | plasma | pancreas | | Cmax(ng/mL) | 3990±390 | 12216±1509 | | AUC0-t(ng/mL*h) | 13621±2127 | 51394±10098 | | Cl(mL/h/kg) | 3734±641 | 996±189 |
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| Animal Model: | T1D mouse models and T2D mouse models[1] | | 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 low HbA1c and a good antidiabetic effect, improved the histological structure of the islet. |
| Animal Model: | mice, Sprague Dawley rats, and beagle dogs[1] | | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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