KIRA-7, an imidazopyrazine compound, binds the IRE1α kinase (IC50 of 110 nM) to allosterically inhibit its RNase activity. KIRA-7 has an anti-fibrotic effect[1].
KIRA-7 can inhibit XBP1 splicing in the alveolar epithelial cell line MLE12[1].
KIRA-7 (5 mg/kg; intraperitoneal injection; daily for 14 days; C57BL6 mice) treatment results in decreased spliced XBP1 and ATF4, compared to bleomycin exposed mice treated with vehicle. Likewise, mRNA levels of BiP and CHOP are significantly elevated after Bleomycin exposure, and treatment of Bleomycin-exposed mice with KIRA-7 decreased these levels. mRNA levels of collagen 1A1 and fibronectin are both significantly decreased by KIRA-7 treatment[1].
[1]. Thamsen M, et al. Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung. PLoS One. 2019 Jan 9;14(1):e0209824.