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BU wins $1.6M NIH grant to target protein-protein interactions

(Boston) An interdisciplinary team of Boston University professors is launching a project to develop new ways to target protein-protein interactions with synthetic organic drugs. Financed by a four-year $1.6 million grant from the National Institutes of Health, the goal is to develop new approaches for discovering "drug-like" small molecule inhibitors against challenging protein-protein interaction (PPI) interfaces.

Only about 10% of the potential drug targets in the human genome have been successfully targeted with marketed drugs. Of the remaining 90%, a large proportion are intracellular proteins whose function is critically dependent on their reversible interactions with other proteins. Despite decades of effort by the pharmaceutical industry, it has proven extraordinarily difficult to develop oral drugs that inhibit PPI.

The work will determine if appropriately designed synthetic macrocycles can inhibit PPI targets while maintaining good drug-like properties. The test system is the intracellular PPI target NFB essential modulator (NEMO), a component of the Inhibitor of B kinase (IKK) complex. Chronic hyperactivity of the NFB pathway is found in human inflammatory diseases and cancers. Inhibiting the interaction of NEMO with IKK, as a more targeted alternative to completely ablating all IKK kinase activity, represents a promising new approach for attenuating inflammation.

Led by College of Arts & Sciences Professor Adrian Whitty (quantitative biochemistry and drug discovery), the multidisciplinary research team includes Profs. Sandor Vajda and Dima Kozakov (computational chemistry), John Porco and Aaron Beeler (macrocycle design and synthesis), Karen Allen (X-ray crystallography), and Tom Gilmore (NF-B pathway biology). Their grant is funded by the NIH's National Institute of General Medical Sciences.


Contact: Patrick Farrell
Boston University Medical Center

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