a16z Podcast Undruggable Drugs
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May 6, 2020 Jay Bradner, President of the Novartis Institute for BioMedical Research, reveals cutting-edge advancements in drug development. He discusses the challenges of targeting 'undruggable' proteins and how innovative techniques like molecular glues and gene therapies are revolutionizing therapeutic possibilities. Bradner shares breakthroughs focused on previously inaccessible targets, like SHIP2, and emphasizes the importance of collaboration in this field. Insights into the science behind drug discovery shine a light on the future of treatment for serious diseases.
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Undruggable Targets Defined
- "Undruggable" targets are proteins or RNA sequences currently impossible to drug.
- This often means they lack a suitable "pocket" for traditional small molecule drugs to bind.
Understanding vs. Approaching Targets
- Undruggable targets are not always due to a lack of biological understanding.
- The challenge lies in finding ways to approach and interact with these targets, like MYC in cancer.
SHIP2: An "Undruggable" Success
- Novartis developed the first inhibitor of a phosphatase, SHIP2, previously considered "undruggable."
- This was achieved by targeting an allosteric site instead of the active site, effectively "gluing" the protein.