KIRA6

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

KIRA6 是 IRE1α RNase 激酶的有效抑制剂 (IC50: 0.6 μM)。它可以触发细胞凋亡反应。KIRA6（10-1000 nM，72 小时）在低 nM 浓度下强烈损害 KIT 依赖性细胞系 HMC-1.1 的活力，其方式与 KIT 阻断一致。

KIRA6 is an effective inhibitor of IRE1α RNase kinase (IC50: 0.6 μM). It can trigger an apoptotic response.KIRA6 (10-1000 nM, 72 hours) strongly compromises the viability of the KIT-dependent cell line HMC-1.1 at the low nM concentration, in a manner that coincided with KIT blockade. KIRA6 (1nM-100μM) bounds to the cytoplasmic domain of KIT with a Kd value of 10.8 ?μM. KIRA6 (10-1000 nM, 1 hour) reduces signaling output of KIT, including the phosphorylation of KIT as well as its downstream signaling modules, PSTAT5 and phosphorylated ERK1/2.KIRA6 (1 μM, 0-48 hours) inhibits Ins1 mRNA decay from IRE1α hyperactivation in a dose-dependent manner. KIRA6 (0.1-10μM, 72 hours) dose-dependently reduces 1NM-PP1 potentiation of Ins1 apoptosis during ER stress in a dose-dependent manner [2].KIRA6 (intraperitoneal injection; 5 mg/kg; 37 days) shows significant amelioration of random glucose levels over several weeks compared to the vehicle, both fed ad lib. KIRA6 (i.p, 5 mg/kg, 21 or 18 days post injections) increases both plasma insulin and C-peptide levels, remains insulin-positive islet areas at a high level after stopping injections in the Akita Mouse.

Cell Viability Assay Cell Line:HMC-1.1 cellsConcentration:10 nM, 30 nM, 100 nM, 300 nM, 1000 nM Incubation Time:72 hours Result:Inhibited cell viability from 30 nM.Western Blot Analysis Cell Line:HMC-1.1 cells Concentration:10 nM, 30 nM, 100 nM, 300 nM, 1000 nM Incubation Time:1 hours Result:Reduced expression of phosphorylated KIT, STAT5 and ERK1/2.RT-PCRCell Line:INS-1 IRE1α (WT) cells Concentration:1 μM Incubation Time: 0 hour, 12 hours, 24 hours, 48 hours Result:Inhibited Ins1 mRNA expression.Apoptosis Analysis Cell Line:INS-1 IRE1α (WT) cells Concentration:1-10 μM Incubation Time:72 hours Result:Reduced 1NM-PP1 potentiation of Ins1 apoptosis during ER stress.

Animal Model:Male Ins2+/Akita miceDosage:5 mg/kg Administration:Intraperitoneal injection; 5 mg/kg; 21 or 18 days postinjections Result:Attenuates b cell functional loss, increased insulin levels.

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Others

Other Targets

IRE1α

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1589527-65-0

518.53

C28H25F3N6O

>98% (HPLC)

DMSO:5 mg/mL (9.64 mM);Ethanol:2 mg/mL (3.86 mM; Need ultrasonic)

CC(C)(C)C1=NC(=C2N1C=CN=C2N)C1=CC=C(NC(=O)NC2=CC=CC(=C2)C(F)(F)F)C2=CC=CC=C12

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(-20℃)

With Ice Pack

≥ 2 years