Robust Generation of Lead Compounds for Protein–Protein Interactions by Computational and MCR Chemistry: p53/Hdm2 Antagonists


  • MCR: multicomponent reaction. We thank Dr. Ulli Rothweiler for fruitful discussion. This work was supported by the NIH (grant 1R21M087617-01 to A.D.) and the Deutsche Krebshilfe (grant 108354 to T.H.) and is part of an NCI-RAND program. We thank Haixia Liu for the synthesis of PB3.


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The parallel discovery of multiple scaffolds useful to antagonize the cancer-relevant protein–protein interaction p53/Hdm2 is described. The new method is based on the tightly interwoven interplay of multicomponent reaction chemistry, structural biology, computational chemistry, and high-content NMR-based screening.