KIRA6

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.