CAS NO: | 1589527-65-0 |
包装 | 价格(元) |
1mg | 电议 |
5mg | 电议 |
10mg | 电议 |
Cas No. | 1589527-65-0 |
Canonical SMILES | O=C(NC1=CC=CC(C(F)(F)F)=C1)NC2=C3C=CC=CC3=C(C4=C5C(N)=NC=CN5C(C(C)(C)C)=N4)C=C2 |
分子式 | C28H25F3N6O |
分子量 | 518.53 |
溶解度 | DMSO : ≥ 5 mg/mL (9.64 mM);Ethanol : 2 mg/mL (3.86 mM) |
储存条件 | Store at -20°C |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
产品描述 | 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]. References: |