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Updated: Oct 24, 2025

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

Katherine L Jones1, Dominic M Beaumont1, Sharon G Bernard1

  • 1GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, U.K.

Journal of Medicinal Chemistry
|August 13, 2021
PubMed

Insights

Researchers optimized the bromodomain and extra terminal (BET) protein inhibitor I-BET151 into I-BET282E. This new molecule shows improved properties for clinical development in oncology and inflammatory diseases.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Bromodomain and extra terminal (BET) proteins play crucial roles in diseases, especially oncology and immuno-inflammatory conditions.
  • Existing BET inhibitors face attrition risks due to toxicity, necessitating novel chemical series.

Purpose of the Study:

  • To optimize the in vivo tool molecule I-BET151 into a candidate suitable for clinical studies.
  • To develop novel BET inhibitors from distinct chemical series to mitigate toxicity risks.

Main Methods:

  • Structure- and property-based drug design and optimization.
  • Lead optimization of I-BET151 towards I-BET282E.

Main Results:

  • Successful optimization of I-BET151 to I-BET282E.
  • I-BET282E exhibits properties suitable for clinical progression.

Conclusions:

  • I-BET282E represents a promising next-generation BET inhibitor.
  • This optimized molecule addresses the need for novel BET inhibitors with improved safety profiles for clinical application in cancer and inflammatory diseases.

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