Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer

• DOI: 10.1002/cmdc.201700447
• Publication Date: 2017-09-29T16:52:36Z
• Authors: Ulrich Lücking; Arne Scholz; Philip Lienau; Gerhard Siemeister; Dirk Kosemund; Rolf Bohlmann; Hans Briem; Ildiko Terebesi; Kirstin Meyer; Katja Prelle; Karsten Denner; Ulf Bömer; Martina Schäfer; Knut Eis; Ray Valencia; Stuart Ince; Franz von Nussbaum; Dominik Mumberg; Karl Ziegelbauer; Bert Klebl; Axel Choidas; Peter Nussbaumer; Matthias Baumann; Carsten Schultz‐F...; Gerd Rühter; Jan Eickhoff; Michael Brands
• Keywords: Tolerability

Abstract Selective inhibition of exclusively transcription‐regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY‐958, optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited best overall profile vitro vivo, including high efficacy good tolerability xenograft models mice rats. first potent highly selective inhibitor enter trials for treatment cancer.