CG-4-209

CG-4-209 is a novel polypharmacologic dual BCL-2/FLT3 hybrid single-molecule inhibitor designed for the treatment of acute myeloid leukemia (AML). It was developed by tethering the BCL-2 inhibitor venetoclax (VEN) to the FLT3 inhibitor gilteritinib (GIL) through their solvent-exposed domains. The rationale behind this hybrid approach is to offer superior therapeutic results compared to the corresponding polypharmacy approach (the combination of two separate drugs) by ensuring simultaneous inhibition of both targets within the same cell. However, preclinical studies have indicated that while CG-4-209 and similar hybrids exhibit antileukemic activity, the two-drug combination of venetoclax and gilteritinib remains more active in AML cell models. CG-4-209 is primarily being investigated in the context of AML, particularly cases characterized by FLT3 mutations and BCL-2 overexpression.

Other names

VEN-GIL hybrid inhibitor