2. Academic Validation
  3. Changing for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for Once Weekly Intravenous Dosing for the Treatment of Cancer

Changing for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for Once Weekly Intravenous Dosing for the Treatment of Cancer

  • J Med Chem. 2021 Aug 12;64(15):11651-11674. doi: 10.1021/acs.jmedchem.1c01000.
Ulrich Lücking 1,  Dirk Kosemund 1,  Niels Böhnke 1,  Philip Lienau 1,  Gerhard Siemeister 1,  Karsten Denner 1,  Rolf Bohlmann 1,  Hans Briem 1,  Ildiko Terebesi 1,  Ulf Bömer 1,  Martina Schäfer 1,  Stuart Ince 1,  Dominik Mumberg 1,  Arne Scholz 1,  Raquel Izumi 2,  Stuart Hwang 2,  Franz von Nussbaum 1
Affiliations

Affiliations

  • 1 Pharmaceuticals, Research and Development, Bayer Pharma AG, Müllerstr. 178, Berlin 13353, Germany.
  • 2 Vincerx Pharma, Inc., 260 Sheridan Avenue, Suite 400, Palo Alto, California 94306, United States.
PMID: 34264057 DOI: 10.1021/acs.jmedchem.1c01000
Abstract

Selective inhibition of exclusively transcription-regulating positive transcription elongation factor b/CDK9 is a promising new approach in Cancer therapy. Starting from atuveciclib, the first selective CDK9 Inhibitor to enter clinical development, lead optimization efforts aimed at identifying intravenously (iv) applicable CDK9 inhibitors with an improved therapeutic index led to the discovery of the highly potent and selective clinical candidate VIP152. The evaluation of various scaffold hops was instrumental in the identification of VIP152, which is characterized by the underexplored benzyl sulfoximine group. VIP152 exhibited the best preclinical overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats upon once weekly iv administration. VIP152 has entered clinical trials for the treatment of Cancer with promising longterm, durable monotherapy activity in double-hit diffuse large B-cell lymphoma patients.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z