Asnuciclib (CDKI-73) is a potent CDK9 inhibitor with Ki of 4 nM, shows cytotoxicity against a broad CLL samples with mean LD50 of 80 nM.
CDKI-73 induces caspase-dependent apoptosis that was preceded by dephosphorylation of CDK9 and serine 2 of RNA polymerase II.
CDKI-73 is more potent than the pan-CDK inhibitor Flavopiridol and shows >200-fold selectivity against primary leukemia cells when compared with normal CD34+ cells.
CDKI-73 shows cytotoxic synergy with the nucleoside analog fludarabine in in poor prognostic sub-groups of leukemia patients, which is associated with CDKI-73-mediated transcriptional inhibition of MCL1 and XIAP.
