fadraciclib + azacitidine

Fadraciclib + azacitidine is a combination of two agents: fadraciclib, a selective cyclin-dependent kinase 2/9 (CDK2/9) inhibitor, and azacitidine, a DNA methyltransferase inhibitor (hypomethylating agent). Fadraciclib inhibits CDK2 and CDK9, resulting in cell cycle arrest and suppression of RNA polymerase II-dependent transcription, thereby inducing apoptosis and downregulating the anti-apoptotic protein myeloid cell leukemia 1 (MCL-1). Azacitidine incorporates into DNA and RNA, causing hypomethylation of DNA, cellular differentiation, and cytotoxicity in abnormal hematopoietic cells. Preclinical studies indicate that the combination exhibits synergistic antileukemic activity in acute myeloid leukemia (AML), with a favorable therapeutic window for AML cells but limited cytotoxicity on normal hematopoietic cells. Fadraciclib is developed by Cyclacel and is being studied in AML both as monotherapy and in combination with azacitidine[1][3][5].