Advancements in Cancer Therapy: The Development and Efficacy of BAY 1251152, a Selective PTEFb Inhibitor

The transcription of short-lived proteins like Mcl-1 and Myc, which are crucial for the growth and survival of cancer cells, is significantly influenced by PTEFb/CDK9. These proteins are also key in the development of resistance to chemotherapy. We have previously reported on BAY 1143572, a selective PTEFb/CDK9 inhibitor that has shown promising results in preclinical studies and has entered clinical trials. This compound demonstrated potent activity against PTEFb/CDK9, selectivity against other CDKs, and broad anti-proliferative effects against various tumor cell lines.

In pursuit of more potent treatments, we initiated a program to identify new PTEFb/CDK9 inhibitors. Through extensive optimization, we discovered BAY 1251152, which exhibits enhanced biochemical and cellular potency, increased selectivity, and desirable pharmacokinetic properties. This compound has shown excellent efficacy in xenograft models when administered intravenously and is currently being evaluated in Phase I clinical trials to assess its safety, tolerability, pharmacokinetics, and initial pharmacodynamic biomarker response in patients with advanced cancer.

This presentation will reveal the structure of BAY 1251152 for the first time and discuss the key findings from our optimization program for PTEFb/CDK9 inhibitors. The research was conducted by a team of scientists and presented at the American Association for Cancer Research Annual Meeting in 2017.