| Description |
Kira8 is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α’s RNase[1].
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| Related Catalog |
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| Target |
IRE1α[1]
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| In Vitro |
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].
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| In Vivo |
Kira8 efficaciously reverses established diabetes in NOD mice by sparing β-cells and preserving their physiological function. KIRA8 is first tested in 3-week-old male pre-diabetic Akita mice by i.p. daily dosing of 50 mg/kg, whereupon significant reduction of hyperglycemia became apparent over several weeks. Then KIRA8 (50 mg/kg) is tested in the complex NOD. Showing target engagement, one week treatment of pre-diabetic NODs with KIRA8 leads to significant reductions in islet XBP1 splicing and TXNIP mRNAs, and preserved Ins1/Ins2, BiP and MANF mRNAs[1].
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| References |
[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.
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