1630086-20-2

1630086-20-2 structure

Name: Kira8
Chemical Name: Kira8
CAS Number: 1630086-20-2
Molecular Formula: C₃₁H₂₉ClN₆O₃S
Molecular Weight: 601.12
Catalog: Signaling Pathways Cell Cycle/DNA Damage IRE1
Create Date: 2019-03-03 12:19:00
Modify Date: 2024-01-31 16:36:51
Kira8 is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α’s RNase[1].

Name	Kira8

Description	Kira8 is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α’s RNase[1].
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> IRE1 Research Areas >> Inflammation/Immunology
Target	IRE1α[1]
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].
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].
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.