title: How Big Is Too Big for Cell Permeability?
abstract: Understanding how to design cell permeable ligands for intracellular targets that have difficult binding sites, such as protein-protein interactions, would open vast opportunities for drug discovery. Interestingly, libraries of cyclic peptides displayed a steep drop-off in membrane permeability at molecular weights above 1000 Da and it appears likely that this cutoff constitutes an upper size limit also for more druglike compounds. However, chemical space from 500 to 1000 Da remains virtually unexplored and represents a vast opportunity for those prepared to venture into new territories of drug discovery.
authors.affiliation: Department of Pharmacy, BMC, Uppsala University , Box 580, SE-751 23 Uppsala, Sweden.
authors.forename: Pär
authors.identifier: 0000-0002-9094-2581
authors.initials: P
authors.lastname: Matsson
authors.affiliation: Department of Chemistry, BMC, Uppsala University , Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Jan
authors.identifier: 0000-0002-4205-6040
authors.initials: J
authors.lastname: Kihlberg
mesh_terms: D002463:Cell Membrane Permeability / Q000187:drug effects*; D006801:Humans; D008970:Molecular Weight