(±)-Enitociclib

(±)-Enitociclib ((±)-BAY-1251152) is the racemic mixture of Enitociclib (HY-103019E). Enitociclib is a selective CDK9 inhibitor and apoptosis inducer. Enitociclib inhibits CDK9 activity and reduces the phosphorylation of Ser2 in the carboxyl-terminal domain (CTD) of RNA polymerase Pol II, thereby downregulating the transcription of key oncogenes such as MYC and MCL1. Enitociclib has anti-proliferative activity targeting MYC⁺ lymphoma and multiple myeloma (MM) cells, and has synergistic effects with Bortezomib (HY-10227) and Lenalidomide (HY-A0003), and can be used in the research of hematological malignancies^[1][2]. In Vitro:(±)-Enitociclib (12.5-200 nM; 96 h) inhibits cell viability in multiple myeloma (MM) cell lines (NCI-H929, MM1.S, OPM-2, U266B1) in a concentration-dependent manner with an IC₅₀ of 36-78 nM^[2].
(±)-Enitociclib (0.5-1 μM; 6-24 h) induces apoptosis in MM cell lines (NCI-H929, OPM-2), as evidenced by increased cleavage of apoptotic markers caspase-3 and PARP, and down-regulates expression of the anti-apoptotic protein Mcl-1 and oncogenic protein c-Myc^[2]. In Vivo:Enitociclib (15 mg/kg; intravenous injection; once a week; 3 weeks) significantly inhibits tumor growth in mouse multiple myeloma (MM) xenograft models (JJN-3, NCI-H929, OPM-2), reduces tumor volume and prolonged mouse survival^[2].
Enitociclib (15 mg/kg; intravenous injection; once a week) combined with Lenalidomide (HY-A0003) (50 mg/kg, oral, once a day) or Bortezomib (HY-10227) (0.8 mg/kg, intraperitoneal injection, twice a week), synergistically inhibits tumor growth in the OPM-2 xenograft model, with better effect than single factor treatment group^[2].