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**fadraciclib + venetoclax** is a combination therapy of **fadraciclib**, a potent second-generation aminopurine cyclin-dependent kinase (CDK) inhibitor selective for CDK2 and CDK9, and **venetoclax**, a BCL-2 antagonist. Fadraciclib inhibits transcription through CDK9 inhibition, leading to depletion of short-lived anti-apoptotic proteins like Mcl-1 and induction of apoptosis in cancer cells, notably chronic lymphocytic leukemia (CLL)[1][3][5]. Venetoclax selectively targets BCL-2, another anti-apoptotic protein, thus promoting cancer cell death. The combination acts synergistically by concurrently antagonizing Mcl-1 (via fadraciclib) and BCL-2 (via venetoclax), resulting in enhanced apoptosis, overcoming resistance pathways, and showing efficacy in cancer models and cell lines particularly with poor prognosis markers like 17p deletion[1][3][5]. Development is ongoing in hematologic malignancies such as CLL, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and evaluated preclinically in T-cell prolymphocytic leukemia (T-PLL)[1][3][4][5]. The developer for fadraciclib is Cyclacel Pharmaceuticals[1][2][5], and venetoclax is developed by AbbVie and Genentech (Roche).
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