Generation and selection of novel estrogen receptor ligands using the de novo structure-based design tool, SkelGen

Journal of Chemical Information and Modeling

Volumn 46, Issue 2, 2006, Pages 642-647

  Firth Clark, Stuart ^a   Willems, Henriëtte M G ^a   Williams, Anthony ^a   Harris, William ^a  

^a De Novo Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

COMPUTER SYSTEMS PROGRAMMING; CRYSTALLOGRAPHY; MODIFICATION; STRUCTURAL DESIGN; SYNTHESIS (CHEMICAL);

ACTIVE MOLECULES; DE NOVO STRUCTURE; ESTROGEN RECEPTOR (ER) LIGANDS; SKELGEN PROGRAM;

MOLECULAR STRUCTURE;

ESTROGEN RECEPTOR; LIGAND; RECOMBINANT PROTEIN;

ARTICLE; BINDING COMPETITION; BIOLOGICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER PROGRAM; DRUG DESIGN; DRUG POTENTIATION; GENETICS; HUMAN; IC 50; STRUCTURE ACTIVITY RELATION;

BINDING, COMPETITIVE; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; LIGANDS; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; RECEPTORS, ESTROGEN; RECOMBINANT PROTEINS; SOFTWARE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33646237785     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci0502956     Document Type: Conference Paper

References (22)

1. Bohacek, R. S.; McMartin, C. Modern Computational Chemistry and Drug Discovery: Structure Generating Programs. Curr. Opin. Chem. Biol. 1997, 1, 157-161.
2. Han, Q.; Dominguez, C.; Stouten, P. F. W.; Park, J. M.; Duffy, D. E.; Galemmo, R. A.; Rossi, K. A.; Alexander, R. S.; Wong, P. C.; Wright; M. M.; Luettgen, J. M.; Knabb, R. M.; Wexler, R. R. Design, Synthesis and Biological Evaluation of Potent and Selective Amidino Bicyclic Factor Xa Inhibitors. J. Med. Chem. 2000, 43, 4398-4415.
3. Ripka, A. S.; Satyshur, K. A.; Bohacek, R. S.; Rich, D. H. Aspartic Protease Inhibitors Designed from Computer-Generated Templates Bind As Predicted. Org. Lett. 2001, 3, 2309-2312.
4. Honma, T.; Hayashi, K.; Aoyama, T.; Hashimoto, N.; Machida, T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.; Suzuki-Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Morishima, H. Structure-Based Generation of a New Class of Potent Cdk4 Inhibitors: New de novo Design Strategy and Library Design. J. Med. Chem. 2001, 44, 4615-4627.
5. Vinkers, M. H.; de Jonge, M. R.; Daeyaert, F. F. D.; Heeres, J.; Koymans, L. M. H.; van Lenthe, J. H.; Lewi, P. J.; Timmerman, H.; Van Aken, K.; Janssen, P. A. J. SYNOPSIS: SYNthesize and Optimize System in Silico. J. Med. Chem. 2003, 46, 2765-2773.
6. 2 Inhibitors. J. Med. Chem. 1994, 37, 337-341.
7. Grzybowski, B. S.; Ishchenko, A. V.; Kim, C. Y.; Topalov, G.; Chapman, R.; Christianson, D. W.; Whitesides, G. M.; Shaknovich, E. I. Combinatorial computational method gives new picomolar ligands for a known enzyme. PNAS 2002, 99, 1270-1273.
8. Gehlhaar, D. K.; Moerder, K. E.; Zichi, D.; Sherman, C. J.; Ogden, R. C.; Freer, S. T. De Novo Design of Enzyme inhibitors by Monte Carlo Ligand Generation J. Med. Chem. 1995, 38, 466-472.
9. Stahl, M.; Todorov, N. P.; James, T.; Mauser, H.; Boehm, H.-J.; Dean, P. M. A validation study on the practical use of automated de novo design. J. Comput.-Aided Mol. Des. 2002, 16, 459-478.
10. Todorov, N. P.; Dean, P. M. A branch-and-bound method for optimal atom-type assignment in de novo ligand design. J. Comput.-Aided Mol. Des. 1998, 12, 335-349.
11. Todorov, N. P.; Dean, P. M. Evaluation of a method for controlling molecular scaffold diversity in de novo ligand design. J. Comput.-Aided Mol. Des. 1997, 11, 175-192.
12. Meegan, M. J.; Lloyd, D. G. Advances in the science of estrogen receptor Modulation. Curr. Med. Chem. 2003, 10, 181-210.
13. Sato, M.; Grese, T. A.; Dodge, J. A.; Bryant, H. U.; Turner, C. H. Emerging Therapies for the prevention or treatment of postmenopausal osteoporosis. J. Med. Chem. 1999, 42, 1 -24.
14. InsightII/DISCOVER; Cerius2; Accelrys: San Diego, CA.
15. Stahl, M.; Rarey, M. Detailed analysis of scoring functions for virtual screening. J. Med. Chem. 2001, 44, 1035-1042.
16. SMARTS; Merlin; Daylight Chemical Information Systems: Mission Viejo, CA.
17. Schopfer, U.; Schoeffter, P.; Bischoff, S. F.; Nozulak, J.; Feuerbach, D.; Floersheim, P. Toward Selective ERa Agonists for Central Nervous System Disorders: Synthesis and Cnaracterization of Aryl Benzthiophenes. J. Med. Chem. 2002, 45, 1399-1401.
18. von Angere, E.; Prekajac, J.; Strohmeier, J. 2-Phenylindoles. Relationship between structure, estrogen receptor affinity, and mammary tumor inhibiting activity in the rat. J. Med. Chem. 1984, 27, 1439-1447.
19. Registry: highest RN 790189-55-8; Chemical Abstracts Service: Columbus, Ohio. http://www.cas.org/ONLINE/DBSS/registryss.html (accessed June 2004).
20. MARPAT: Vol. 141, Iss. 22; Chemical Abstracts Service: Columbus, Ohio. http://www.cas.org/ONLINE/DBSS/marpatss.html (accessed June 2004).
21. MARPATPREV: 20041130/ED; Chemical Abstracts Service: Columbus, Ohio. http://www.cas.org/ONLINE/DBSS/marpatprevss.html (accessed June 2004).
22. Beilstein: 2004/11/03/ED; Chemical Abstracts Service: Columbus, Ohio. http://www.cas.org/ONLINE/DBSS/Beilsteinss.html (accessed June 2004).