title: Two- and three-dimensional quantitative structure-activity relationships studies on a series of liver x receptor ligands.
abstract: Liver X receptor (LXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidaemia and cholestasis. In the present work, comparative molecular field analysis (CoMFA) and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent LXR ligands. Significant correlation coefficients (CoMFA, r(2) = 0.98 and q(2) = 0.69; HQSAR, r(2) = 0.99 and q(2) = 0.85) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contribution maps should be useful for the design of novel LXR ligands having improved potency.
authors.affiliation: Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, Av. Arlindo Bettio, 1000, 03828-000, São Paulo, SP, Brazil.
authors.forename: Káthia M
authors.initials: KM
authors.lastname: Honório
authors.forename: Lívia B
authors.initials: LB
authors.lastname: Salum
authors.forename: Richard C
authors.initials: RC
authors.lastname: Garratt
authors.forename: Igor
authors.initials: I
authors.lastname: Polikarpov
authors.forename: Adriano D
authors.initials: AD
authors.lastname: Andricopulo
references.citation: J Mol Graph Model. 2007 Sep;26(2):434-42
references.pmid: 17349808
references.citation: Mol Endocrinol. 2005 Jun;19(6):1429-38
references.pmid: 15914712
references.citation: J Med Chem. 2001 Mar 15;44(6):886-97
references.pmid: 11300870
references.citation: Annu Rev Physiol. 2003;65:261-311
references.pmid: 12518001
references.citation: J Am Chem Soc. 1988 Aug 1;110(18):5959-67
references.pmid: 22148765
references.citation: J Mol Biol. 2003 Dec 12;334(5):853-61
references.pmid: 14643652
references.citation: Cell Mol Life Sci. 2006 Mar;63(5):524-39
references.pmid: 16389454
references.citation: Trends Endocrinol Metab. 2006 Sep;17(7):284-90
references.pmid: 16870465
references.citation: J Comput Aided Mol Des. 2004 Jul-Sep;18(7-9):587-96
references.pmid: 15729857
references.citation: Nat Rev Drug Discov. 2004 Nov;3(11):950-64
references.pmid: 15520817
references.citation: J Biol Chem. 2003 Oct 3;278(40):38821-8
references.pmid: 12819202
references.citation: Bioorg Med Chem. 2006 Jan 15;14(2):516-27
references.pmid: 16203153
references.citation: Bioorg Med Chem Lett. 2005 Jun 15;15(12):3119-25
references.pmid: 15893927
references.citation: SAR QSAR Environ Res. 2007 Oct-Dec;18(7-8):711-27
references.pmid: 18038369
references.citation: Mol Endocrinol. 2003 Jun;17(6):985-93
references.pmid: 12690094
references.citation: Comb Chem High Throughput Screen. 2006 Nov;9(9):683-9
references.pmid: 17100573
references.citation: J Mol Graph Model. 2007 Mar;25(6):921-7
references.pmid: 17055759
references.citation: J Comput Aided Mol Des. 2004 Jul-Sep;18(7-9):563-76
references.pmid: 15729855
references.citation: Nat Med. 2002 Nov;8(11):1243-8
references.pmid: 12411951
references.citation: J Nutr Biochem. 2003 Oct;14(10):554-67
references.pmid: 14559106
references.citation: Genes Dev. 1998 Oct 15;12(20):3149-55
references.pmid: 9784489
references.citation: J Lab Clin Med. 2003 Jul;142(1):7-20
references.pmid: 12878981
references.citation: J Med Chem. 2002 May 9;45(10):1963-6
references.pmid: 11985463