Structure-based virtual screening for plant-based ERβ-selective ligands as potential preventative therapy against age-related neurodegenerative diseases

被引：78

作者：

Zhao, LQ

Brinton, RD ^{[1
]}

机构：

[1] Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA

[2] Univ So Calif, Sch Pharm, Program Neurosci, Los Angeles, CA 90089 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 10期

关键词：

D O I：

10.1021/jm0490538

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

ER beta has been associated with estrogen-induced promotion of memory function and neuronal survival. Based on the optimized complex structure of human ER beta LBD bound with genistein, computer-aided. structure-based virtual screening against a natural source chemical database was conducted to determine the occurrence of plant-based ER beta-selective ligands. Twelve representative hits derived from database screening were assessed for their binding profiles to both ERs, three of which displayed over 100-fold binding selectivity to ER beta over ER alpha.

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收藏

页码：3463 / 3466

页数：4

相关论文

共 24 条

[1] Impact of estrogen therapy on Alzheimer's disease - A fork in the road? [J].

Brinton, RD .

CNS DRUGS, 2004, 18 (07) :405-422

[2] Estrogen receptor null mice: What have we learned and where will they lead us? [J].

Couse, JF ;

Korach, KS .

ENDOCRINE REVIEWS, 1999, 20 (03) :358-417

[3] Conjugated equine estrogens and global cognitive function in postmenopausal women - Women's Health Initiative Memory Study [J].

Espeland, MA ;

Rapp, SR ;

Shumaker, SA ;

Brunner, R ;

Manson, JE ;

Sherwin, BB ;

Hsia, J ;

Margolis, KL ;

Hogan, PE ;

Wallace, R ;

Dailey, M ;

Freeman, R ;

Hays, J .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 291 (24) :2959-2968

[4] What pharmacologists can learn from recent advances in estrogen signalling [J].

Gustaftson, JÅ .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2003, 24 (09) :479-485

[5] Development and validation of a genetic algorithm for flexible docking [J].

Jones, G ;

Willett, P ;

Glen, RC ;

Leach, AR ;

Taylor, R .

JOURNAL OF MOLECULAR BIOLOGY, 1997, 267 (03) :727-748

[6] Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women - A randomized controlled trial [J].

Kreijkamp-Kaspers, S ;

Kok, L ;

Grobbee, DE ;

de Haan, EHF ;

Aleman, A ;

Lampe, JW ;

van der Schouw, YT .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2004, 292 (01) :65-74

[7] Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors α and β [J].

Mäkelä, S ;

Savolainen, H ;

Aavik, E ;

Myllärniemi, M ;

Strauss, L ;

Taskinen, E ;

Gustafsson, JÅ ;

Häyry, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :7077-7082

[8] Estrogen receptor-β potency-selective ligands:: Structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues [J].

Meyers, MJ ;

Sun, J ;

Carlson, KE ;

Marriner, GA ;

Katzenellenbogen, BS ;

Katzenellenbogen, JA .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (24) :4230-4251

[9] ER beta: Identification and characterization of a novel human estrogen receptor [J].

Mosselman, S ;

Polman, J ;

Dijkema, R .

FEBS LETTERS, 1996, 392 (01) :49-53

[10] Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist [J].

Pike, ACW ;

Brzozowski, AM ;

Hubbard, RE ;

Bonn, T ;

Thorsell, AG ;

Engström, O ;

Ljunggren, J ;

Gustafsson, JK ;

Carlquist, M .

EMBO JOURNAL, 1999, 18 (17) :4608-4618