CDK9
CDK9 is a cyclin dependent kinase and an essential regulator of cancer-promoting transcriptional programs and an important driver in Myc-driven solid tumors and hematologic malignancies. PRT2527 is a potent and highly selective CDK9 inhibitor currently being evaluated in a Phase 1 dose escalation study in patients whose cancers are likely to be dependent on CDK9.
Targeting CDK9
Cyclin-dependent kinase 9, or CDK9, serves as a key regulator of several cancer-promoting transcriptional programs, including those driven by MCL1, MYC, and MYB. Inhibition of CDK9 has emerged as an attractive therapeutic approach to selectively target cancers that are transcriptionally addicted to cancer-promoting proteins like MYC and MCL1, and several non-selective CDK9 inhibitors in development have demonstrated activity in multiple tumor types. However, the approach has been significantly limited due to adverse effects associated with broad kinase inhibition, and in turn, a narrow therapeutic window.
Highly Selective, ATP Competitive CDK9 Inhibitor
PRT2527
Prelude is developing PRT2527, which is designed to be a potent and selective CDK9 inhibitor. PRT2527 was shown to reduce MCL1 and MYC protein levels and was highly active in preclinical models at well-tolerated doses. PRT2527 has demonstrated high potency and kinase selectivity which may offer improved efficacy and safety compared to less selective CDK9 inhibitors.