Kira8 Hydrochloride (AMG-18 Hydrochloride) is a mono-selectiveIRE1αinhibitor that allosterically attenuatesIRE1α RNase activitywith anIC₅₀of 5.9 nM^[1].

IRE1α^[1]
IC50: 5.9 nM (IRE1α RNase)^[1]

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^[1].

MaleIns2^+/Akitamice are injected i.p. with KIRA8 (50 mg/kg; daily; for 35 days), significant reduction of hyperglycemia become apparent over several weeks^[1].
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^[1].

637.58

C₃₁H₃₀Cl₂N₆O₃S

2250019-92-0

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.