Kira8 (AMG-18) is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α RNase activity with an IC50 of 5.9 nM.
IC50&Target
IRE1α
IC50: 5.9 nM (IRE1α RNase)
体外研究
Kira8 blocks IRE1α oligomerization, and potently inhibits IRE1α RNase activity against XBP1 and Ins2 RNAs. Kira8 more potently reduces IRE1α-driven apoptosis in INS-1 cells than KIRA6 and also reverses XBP1 splicing promoted by GNF-2.
体内研究
Male Ins2 mice are injected i.p. with KIRA8 (50 mg/kg; daily; for 35 days), significant reduction of hyperglycemia become apparent over several weeks.
One week treatment of pre-diabetic NODs mice with Kira8 (50 mg/kg; i.p.; once a day) leads to significant reductions in islet XBP1 splicing and TXNIP mRNAs, and preserves Ins1/Ins2, BiP and MANF mRNAs.
Animal Model:
Male Ins2 mice
Dosage:
50 mg/kg
Administration:
Injected i.p.; daily; for 35 days
Result:
Significant reduction of hyperglycemia became apparent over several weeks.
分子式
C31H29ClN6O3S
分子量
601.12
CAS号
1630086-20-2
运输条件
Room temperature in continental US; may vary elsewhere.