Topological polar surface area defines substrate transport by multidrug resistance associated protein 1 (MRP1/ABCC1).
Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while those with low TPSA are not. The conjugation to GSH increases TPSA values favoring transport. A strong correlation between TPSA and transport properties (K(m)) was also found.
Fernandes
Janaina
J
Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunologia Celular, Universidade Federal do Rio de Janeiro, 21949-900 Rio de Janeiro, Brazil. janainaf@biof.ufrj.br
Gattass
Cerli R
CR
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001692:Biological Transport; D005978:Glutathione; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005978:Glutathione; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1