Two chemically distinct CDK8/19 inhibitors - Senexin B and Snx631 prevented nuclear envelope breakdown and first polar body extrusion, blocking key molecular events required for exiting the dictyate - inhibition of PKA activity and activation of the CDK1/Cyclin B complex. Notably, these effects appear to be independent of roles of CDK8/19 in transcription, which is not required for resumption of meiosis. These findings for the first time demonstrate the roles of CDK8/19 activity in oocyte maturation, through its role in transcription-independent regulation of PKA activity.

These findings prove the highly synergistic mechanism of action of RVU120+VEN combination and the potential to overcome primary/acquired VEN resistance in relapse/refractory AML disease. Altogether, the presented results support ongoing clinical studies evaluating romaciclib and VEN in VEN/HMA-refractory patients ( NCT06191263 ) and provide a basis for future exploration as a frontline therapy in VEN-naïve patients.

P2, N=10, Not yet recruiting, Ryvu Therapeutics SA | Initiation date: Aug 2025 --> Dec 2025