The blood-brain barrier (BBB) poses a significant obstacle in developing therapeutics for neurodegenerative diseases and central nervous system (CNS) disorders. P-glycoprotein (P-gp), a multidrug resistance protein, is a critical gatekeeper at the BBB and plays a role in cancer chemoresistance. Jay Conrad, Nick A. Paras, and Roy J. Vaz of IND’s Prusiner lab used cryo-EM P-gp structures as starting points with an induced fit docking (IFD) model to model substrate P-gp interactions aiding in the design of drugs for neurodegenerative disorders and cancer therapies.

Reference: Jay Conrad, Nick A. Paras, and Roy J. Vaz

Journal of Medicinal Chemistry 2024 ASAP

DOI: 10.1021/acs.jmedchem.4c00139