CG-4-210

CG-4-210 is a polypharmacologic small molecule hybrid inhibitor that integrates the structural motifs of the BCL-2 inhibitor venetoclax and the FLT3 inhibitor gilteritinib. Developed by researchers at the University of Maryland, the compound was designed to address the heterogeneity of acute myeloid leukemia (AML) by simultaneously targeting two critical survival pathways: the anti-apoptotic protein BCL-2 and the Fms-like tyrosine kinase 3 (FLT3). CG-4-210 was synthesized by tethering the two parent inhibitors through their solvent-exposed domains. Although the hybrid molecule demonstrates dual inhibitory activity, preclinical evaluations in AML cell lines indicated that the polypharmacy combination of separate venetoclax and gilteritinib treatments remained more potent than the single-molecule hybrid approach.