Cdk9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma

HIGHLIGHTS

SUMMARY

    The cyclin-dependent kinase (CDK) family of proteins plays an integral role in the regulation of cell cycle progression (e_g, CDK1/2/4/6) and RNA transcription (e_g, CDK7/8/9/11). AZD4573, a clinical congener of AZ5576, was shown to suppress transcription of the pro-survival proteins Mcl-1 and Bfl-1/A1 in lymphoid tumors, and exhibited anti-tumor effects in AML models in_vivo via an Mcl-1 dependent mechanism. CDK9 inhibition with AZD4573 exhibited pre-clinical efficacy in DLBCL cell lines in_vitro. Considering the relatively short half-life of AZD4573 in_vivo . . .

     

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