Premium
Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer
Author(s) -
Lücking Ulrich,
Scholz Arne,
Lienau Philip,
Siemeister Gerhard,
Kosemund Dirk,
Bohlmann Rolf,
Briem Hans,
Terebesi Ildiko,
Meyer Kirstin,
Prelle Katja,
Denner Karsten,
Bömer Ulf,
Schäfer Martina,
Eis Knut,
Valencia Ray,
Ince Stuart,
von Nussbaum Franz,
Mumberg Dominik,
Ziegelbauer Karl,
Klebl Bert,
Choidas Axel,
Nussbaumer Peter,
Baumann Matthias,
SchultzFademrecht Carsten,
Rühter Gerd,
Eickhoff Jan,
Brands Michael
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700447
Subject(s) - bay , tolerability , in vivo , kinase , pharmacology , chemistry , computational biology , biology , medicine , biochemistry , adverse effect , genetics , civil engineering , engineering
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.