BI033 is a selective small-molecule BTB and CNC homology 1 (BACH1) inhibitor, specifically binds to BACH1 WT with Kd of 9.0 uM, significantly upregulates HO-1 mRNA and protein expression.
BI033 specifically interacts with the N-terminal alanine residue at position 91 within the BTB domain of the BACH1 protein, could not bind to BACH1 91W.
BI033 (1 uM) exhibited a significant increase in HO-1 transcriptional activity in the BACH1 WT overexpressing cells but had a less pronounced effect on HO-1 transcriptional activity in the BACH1 91W overexpressing cells.
BI033 (1 uM) increased VEGFA expression in a time-dependent manner, exhibits greater angiogenic ability on endothelial cells (ECs) than HPPE.
BI033 treatment (1 and 5 mg/kg, i.p.) promotes angiogenesis in the infarcted heart of mice, enhances blood perfusion and angiogenesis in the ischemic hindlimb murine model.
BI033 promotes the expression of proangiogenic genes such as HMOX1 (HO-1), VEGFA, cyclin D1 (CCND1), and activating transcription factor 3 (ATF3) and suppresses inflammatory responses in HUVECs.
BI033 reduces BACH1 nuclear localization and HDAC1 occupancy on BACH1 target genes.