Kira8 Hydrochloride  (Synonyms: AMG-18 Hydrochloride)

Kira8 Hydrochloride (AMG-18 Hydrochloride) is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α RNase activity with an IC₅₀ of 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Male Ins2^+/Akita mice 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

637.58

C₃₁H₃₀Cl₂N₆O₃S

2250019-92-0

O=S(C1=CC=CC=C1Cl)(NC2=C3C=CC(C)=C(C3=CC=C2)OC4=NC=CC=C4C5=NC(N[C@H]6CNCCC6)=NC=C5)=O.[H]Cl

Room temperature in continental US; may vary elsewhere.

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

• [1]. Morita S, et al. Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017 Apr 4;25(4):883-897.e8.  [Content Brief]