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

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

  • ChemMedChem. 2017 Nov 8;12(21):1776-1793. doi: 10.1002/cmdc.201700447.
Ulrich Lücking 1,  Arne Scholz 1,  Philip Lienau 1,  Gerhard Siemeister 1,  Dirk Kosemund 1,  Rolf Bohlmann 1,  Hans Briem 1,  Ildiko Terebesi 1,  Kirstin Meyer 1,  Katja Prelle 1,  Karsten Denner 1,  Ulf Bömer 1,  Martina Schäfer 1,  Knut Eis 1,  Ray Valencia 1,  Stuart Ince 1,  Franz von Nussbaum 1,  Dominik Mumberg 1,  Karl Ziegelbauer 1,  Bert Klebl 2,  Axel Choidas 2,  Peter Nussbaumer 2,  Matthias Baumann 2,  Carsten Schultz-Fademrecht 2,  Gerd Rühter 2,  Jan Eickhoff 2,  Michael Brands 1
Affiliations

Affiliations

  • 1 Bayer AG, Pharmaceuticals Division, Drug Discovery, Müllerstr. 178, 13353, Berlin, Germany.
  • 2 Lead Discovery Center GmbH (LDC), Otto-Hahn-Str. 15, 44227, Dortmund, Germany.
PMID: 28961375 DOI: 10.1002/cmdc.201700447
Abstract

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

Keywords

CDK; PTEFb; antitumor agents; drug design; sulfoximines.

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