Topological polar surface area defines substrate transport by multidrug resistance associated protein 1 (MRP1/ABCC1)

J Med Chem. 2009 Feb 26;52(4):1214-8. doi: 10.1021/jm801389m.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Biological Transport
  • Glutathione
  • Humans
  • Kinetics
  • Models, Chemical*
  • Molecular Conformation
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins
  • Glutathione
  • multidrug resistance-associated protein 1