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KIRA6
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
KIRA6图片
CAS NO:1589527-65-0
规格:98%
分子量:518.53
包装与价格:
包装价格(元)
1mg电议
5mg电议
10mg电议

产品介绍
KIRA6 allosterically inhibits IRE1α RNase kinase activity with an IC50 of 0.6 uM.
CAS:1589527-65-0
分子式:C28H25F3N6O
分子量:518.53
纯度:98%
存储:Store at -20°C

Background:

KIRA6 allosterically inhibits IRE1α RNase kinase activity with an IC50 of 0.6 uM.


KIRA6 dose-dependently inhibits IRE1α (WT) kinase activity, XBP1 RNA cleavage, Ins2 RNA cleavage and oligomerization. KIRA6 strongly inhibits JNK phosphorylation from IRE1α hyperactivation or ER stress. Also, KIRA6 dose-dependently inhibits Ins1 mRNA decay, proinsulin depletion, and apoptosis from IRE1α hyperactivation. In INS-1 cells, KIRA6 inhibits IRE1α auto-phosphorylation by Tg and XBP1 mRNA splicing by Tm in a dose-dependent manner. KIRA6 reduces ER stress-induced death of cultured cells and in pancreatic islet explants[1].


KIRA6 has negligible toxicity up to 10 uM, providing a favorable therapeutic index to test cytoprotection. KIRA6 in BALB/c mice intraperitoneally (i.p.) dosed at 10 mg/kg shows good drug plasma AUC levels with moderate clearance (22.4 mL/min/kg). Drug half-life is 3.90 hours, Cmax is 3.3 uM, and plasma levels at 4 and 8hr are 1.2 uM and 0.33 uM, respectively. Intravitreal co-injection of KIRA6 with Tm significantly reduces XBP1 splicing, TXNIP induction, and decay of the ER-localized photoreceptor-specific Rhodopsin mRNA. KIRA6 dose-dependently inhibits Rhodopsin RNA cleavage by IRE1α. Concomitant with blockage of Terminal UPR outputs, co-injection of KIRA6 in the Tm model reduces photoreceptor loss by Optical Coherence Tomography (OCT) and histology. KIRA6 substantially protects against loss of ERG responsiveness, significantly preserving both a- and b-wave amplitudes[1].


参考文献:
[1]. Ghosh R, et al. Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. 2014 Jul 31;158(3):534-48.