IHMT-MST1-58

• CAT Number: I042863
• CAS Number: 2414484-25-4
• Molecular Formula: C21H22N6O3S
• Molecular Weight: 438.50
• Purity: ≥95%
• Synonyms: 4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide
• InChI: InChI=1S/C21H22N6O3S/c1-13-6-4-5-7-16(13)18-20(28)26(2)17-12-23-21(25-19(17)27(18)3)24-14-8-10-15(11-9-14)31(22,29)30/h4-12,18H,1-3H3,(H2,22,29,30)(H,23,24,25)
• InChIKey: FWEIAKDAIDQPRK-UHFFFAOYSA-N
• SMILES: CC1=CC=CC=C1C2C(=O)N(C3=CN=C(N=C3N2C)NC4=CC=C(C=C4)S(=O)(=O)N)C

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[1].
IHMT-MST1-58 (compound 19) shows good activity against MST1 with an IC50 value 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 Kd values 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].
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

Reference

[1]. Yun Wu, et al. Discovery of IHMT-MST1-58 as a Novel, Potent, and Selective MST1 Inhibitor for the Treatment of Type 1/2 Diabetes. J Med Chem. 2022 Sep 8;65(17):11818-11839
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