2. Academic Validation
  3. Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression

Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression

  • J Med Chem. 2021 Aug 26;64(16):12200-12227. doi: 10.1021/acs.jmedchem.1c00855.
Katherine L Jones 1,  Dominic M Beaumont 1,  Sharon G Bernard 1,  Rino A Bit 1,  Simon P Campbell 1,  Chun-Wa Chung 1,  Leanne Cutler 1,  Emmanuel H Demont 1,  Kate Dennis 1,  Laurie Gordon 1,  James R Gray 1,  Michael V Haase 1,  Antonia J Lewis 1,  Scott McCleary 1,  Darren J Mitchell 1,  Susanne M Moore 1,  Nigel Parr 1,  Olivia J Robb 1,  Nicholas Smithers 1,  Peter E Soden 1,  Colin J Suckling 2,  Simon Taylor 1,  Ann L Walker 1,  Robert J Watson 1,  Rab K Prinjha 1
Affiliations

Affiliations

  • 1 GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, U.K.
  • 2 Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow, G1 1XL, U.K.
PMID: 34387088 DOI: 10.1021/acs.jmedchem.1c00855
Abstract

The functions of the bromodomain and extra terminal (BET) family of proteins have been implicated in a wide range of diseases, particularly in the oncology and immuno-inflammatory areas, and several inhibitors are under investigation in the clinic. To mitigate the risk of attrition of these compounds due to structurally related toxicity findings, additional molecules from distinct chemical series were required. Here we describe the structure- and property-based optimization of the in vivo tool molecule I-BET151 toward I-BET282E, a molecule with properties suitable for progression into clinical studies.

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