TY - JOUR
T1 - C@PA: Computer-Aided Pattern Analysis to Predict Multitarget ABC Transporter Inhibitors
AU - Namasivayam, Vigneshwaran
AU - Silbermann, Katja
AU - Wiese, Michael
AU - Pahnke, Jens
AU - Stefan, Sven Marcel
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/3/25
Y1 - 2021/3/25
N2 - Based on literature reports of the last two decades, a computer-aided pattern analysis (C@PA) was implemented for the discovery of novel multitarget ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) inhibitors. C@PA included basic scaffold identification, substructure search and statistical distribution, as well as novel scaffold extraction to screen a large virtual compound library. Over 45,000 putative and novel broad-spectrum ABC transporter inhibitors were identified, from which 23 were purchased for biological evaluation. Our investigations revealed five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA is the very first successful computational approach for the discovery of promiscuous ABC transporter inhibitors.
AB - Based on literature reports of the last two decades, a computer-aided pattern analysis (C@PA) was implemented for the discovery of novel multitarget ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) inhibitors. C@PA included basic scaffold identification, substructure search and statistical distribution, as well as novel scaffold extraction to screen a large virtual compound library. Over 45,000 putative and novel broad-spectrum ABC transporter inhibitors were identified, from which 23 were purchased for biological evaluation. Our investigations revealed five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA is the very first successful computational approach for the discovery of promiscuous ABC transporter inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=85103607490&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.0c02199
DO - 10.1021/acs.jmedchem.0c02199
M3 - Journal articles
C2 - 33724808
AN - SCOPUS:85103607490
VL - 64
SP - 3350
EP - 3366
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 6
ER -