WDB002 / Revolution Medicines - LARVOL DELTA

Molecular Glues Stabilize Water-Mediated Hydrogen Bonds in Ternary Complexes. (PubMed, Chemphyschem) - "In the FKBP12-FRAP-rapamycin complex, two out of three water-mediated hydrogen bonds present in the crystallographic structure are more stable in the presence of the molecular glue, while in the FKBP12-CEP250-WDB002 complex, more water-mediated hydrogen bonds are present in the presence of the molecular glue, and they displayed higher stability. The findings highlight the importance of considering water-mediated hydrogen bonds in developing strategies for the rational design of molecular glues."

Journal • Targeted Protein Degradation • FKBP5 • mTOR

Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface. (PubMed, Proc Natl Acad Sci U S A) - "Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12."

Journal • Infectious Disease • Novel Coronavirus Disease