Kira8 是一种单选择性 IRE1α 抑制剂，可变构减弱 IRE1α RNase 活性，IC50为 5.9 nM。

Kira8 is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α RNase activity (IC50: 5.9 nM).

Kira8 more effectively causes IRE1α-driven apoptosis in INS-1 cells than KIRA6 and also reverses XBP1 splicing promoted by GNF-2. Kira8 blocks IRE1α oligomerization and effectively inhibits IRE1α RNase activity against XBP1 and Ins2 RNAs.

One week of treatment of pre-diabetic NODs mice with Kira8 (50 mg/kg; i.p.; once a day) causes obvious reductions in islet XBP1 splicing and TXNIP mRNAs. It also preserves Ins1/Ins2, BiP, and MANF mRNAs. Male Ins2+/Akita mice are injected i.p. with KIRA8 (50 mg/kg; daily; for 35 days), obviously reduction of hyperglycemia becomes apparent over several weeks.

1630086-20-2

C31H29ClN6O3S

601.12

AMG-18

DMSO:65 mg/mL (108.13 mM),Need ultrasonic
H2O:insoluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years