What is it about?

Protein–protein interactions play essential roles throughout the human body, but are hardly utilized by orally administered medicines. Here we show that the design of rigidly prestructured small molecule medicines can be a broadly applicable intervention strategy for protein-protein-interactions.

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Why is it important?

We revealed rigid prestructuring as the common principle of three chemically diverse protein-protein-interaction inhibitors that progressed to testing in blood cancer patients. Many more disease interventions could be developed following this design strategy.


Many protein-protein-interactions in the human body involve flexible and partially disordered proteins that are better addressed by rigidly preorganised medicines. This intervention opportunity reaches far beyond today’s small molecule medicines.

Dr. Markus Schade
AstraZeneca plc

Read the Original

This page is a summary of: Design of rigid protein–protein interaction inhibitors enables targeting of undruggable Mcl-1, Proceedings of the National Academy of Sciences, May 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2221967120.
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