Abstract
A combinatorial pharmacophore (CP) model for Multidrug and toxin extrusion 1 (MATE1/SLC47A1) inhibitors was developed based on a data set including 881 compounds. The CP model comprises four individual pharmacophore hypotheses, HHR1, DRR, HHR2 and AAAP, which can successfully identify the MATE1 inhibitors with an overall accuracy around 75%. The model emphasizes the importance of aromatic ring and hydrophobicity as two important structural determinants for MATE1 inhibition. Compared with the pharmacophore model of Organic Cation Transporter 2 (OCT2/ SLC22A2), a functional related transporter of MATE1, the hypotheses of AAAP and PRR5 are suggested to be responsible for their ligand selectivity, while HHR a common recognition pattern for their dual inhibition. A series of analysis including molecular sizes of inhibitors matching different hypotheses, matching of representative MATE1 inhibitors and molecular docking indicated that the small inhibitors matching HHR1 and DRR involve in competitive inhibition, while the relatively large inhibitors matching AAAP are responsible for the noncompetitive inhibition by locking the conformation changing of MATE1. In light of the results, a hypothetical model for inhibiting transporting medi...Continue Reading
References
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Dec 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Masato OtsukaYoshinori Moriyama
Jun 30, 2006·Journal of the American Society of Nephrology : JASN·Satohiro MasudaKen-ichi Inui
Nov 25, 2006·Journal of Computer-aided Molecular Design·Steven L DixonRichard A Friesner
May 19, 2007·Biochemical Pharmacology·Yuko TaniharaKen-Ichi Inui
Oct 13, 2007·Proteins·Pascal BenkertDietmar Schomburg
Dec 17, 2008·Science·Satinder K SinghEric Gouaux
Mar 2, 2010·Nature Reviews. Drug Discovery·UNKNOWN International Transporter ConsortiumLei Zhang
Sep 4, 2010·Biochemical Pharmacology·Takanori NakamuraKen-Ichi Inui
Sep 24, 2010·Nature·Xiao HeGeoffrey Chang
Oct 5, 2010·British Journal of Pharmacology·J KönigM F Fromm
Apr 5, 2011·British Journal of Pharmacology·Atsushi Yonezawa, Ken-ichi Inui
May 24, 2011·Journal of Medicinal Chemistry·Yasuto KidoKathleen M Giacomini
Nov 11, 2011·The Journal of Pharmacology and Experimental Therapeutics·Sumito ItoYuichi Sugiyama
Mar 16, 2012·The Journal of Pharmacology and Experimental Therapeutics·Bethzaida AstorgaStephen H Wright
Oct 23, 2012·Clinical Pharmacology and Therapeutics·K M MorrisseyK M Giacomini
Oct 23, 2012·Clinical Pharmacology and Therapeutics·M J Zamek-GliszczynskiK M Hillgren
Dec 18, 2012·Journal of Medicinal Chemistry·Matthias B WittwerKathleen M Giacomini
Mar 20, 2013·Molecular Aspects of Medicine·Hideyuki Motohashi, Ken-ichi Inui
Mar 29, 2013·Nature·Yoshiki TanakaOsamu Nureki
Jun 21, 2013·The Journal of Pharmacology and Experimental Therapeutics·Lucy J Martínez-Guerrero, Stephen H Wright
Oct 25, 2013·Molecular Pharmaceutics·Yuan XuKaixian Chen
Citations
Jul 6, 2016·Molecular Pharmaceutics·Shuangquan WangTingjun Hou
Jul 24, 2020·Journal of Biomolecular Structure & Dynamics·Kartik MitraMukesh Doble
Jul 16, 2016·Molecular Pharmacology·Lucy J Martínez-GuerreroStephen H Wright
Nov 20, 2020·Chemical Communications : Chem Comm·Krishna KumarRavi P Singh
Oct 26, 2018·Organic Letters·Zhi-Hao YouYan-Kai Liu
Sep 3, 2021·Chemical & Pharmaceutical Bulletin·Susumu ShinyaMasaaki Omote