Compound D03 is a potent and selective small-molecule inhibitor of histone methyllysine reader protein chromodomain Y-like (CDYL) with SPR KD of 0.5 uM, disrupts the recruitment of CDYL onto chromatin.
Compound D03 shows excellent selectivity among other chromodomain proteins, including CDYL2 (>140 folds), CDY1 (no observed binding) and CBX7 (>32 folds).
Compound D03 engages with endogenous CDYL, and perturbs the recruitment of CDYL onto chromatin, subsequently resulting in transcriptional derepression of its target genes.
Compound D03 promotes dendritic maturation in primary cultured neurons, consistent with the known ability of CDYL overexpression to restrict dendritic arborization.
Compound D03 (2.5 mg·kg-1·d-1, i.p.) effectively attenuated the kidney dysfunction, pathological damages and tubular pyroptosis without side effects on liver or kidney function and other tissue injuries in cisplatin-induced acute kidney injury mice.