KIRA6

KIRA6 is an advanced small-molecule IRE1α RNase kinase inhibitor with an IC₅₀ of 0.6 µM^[2]. KIRA6 can trigger an apoptotic response^[1]. IC50 & Target:IC50: 0.6 µM (IRE1α RNase kinase)^[2] In Vitro: KIRA6 (1nM-100μM) bounds to the cytoplasmic domain of KIT with a K_d value of 10.8  µM^[1].
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^[1].
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^[1].
KIRA6 (1 μM; 0-48 hours) inhibits Ins1 mRNA decay from IRE1α hyperactivation at a dose-dependent manner^[2].
KIRA6 (0.1-10μM; 72 hours) dose-dependently reduces 1NM-PP1 potentiation of Ins1 apoptosis during ER stress in a dose-dependent manner^[2].
In Vivo: KIRA6 (intraperitoneal injection; 5 mg/kg; 37 days) shows significant amelioration of random glucose levels over several weeks compared to vehicle, both fed ad lib^[2].
KIRA6 (intraperitoneal injection; 5 mg/kg; 21 or 18 days postinjections) increases both plasma insulin and C-peptide levels, remains insulin-positive islet areas at high level after stopping injections in the Akita Mouse^[2].