A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein.
P-glycoprotein (P-gp) functions as a drug efflux pump, mediating multidrug resistance and limiting the efficacy of many drugs. Clearly, identification of potential P-gp substrate liability early in the drug discovery process would be advantageous. We describe a multiple-pharmacophore model that can discriminate between substrates and nonsubstrates of P-gp with an accuracy of 63%. The application of this filter allows large virtual libraries to be screened efficiently for compounds less likely to be transported by P-gp.
Penzotti
Julie E
JE
Lamb
Michelle L
ML
Evensen
Erik
E
Grootenhuis
Peter D J
PD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D006860:Hydrogen Bonding; D019469:Indinavir / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009529:Nicardipine / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019469:Indinavir; D009529:Nicardipine