Molecular modeling in the discovery of drug leads

Journal of Chemical Information and Computer Sciences

Volumn 36, Issue 4, 1996, Pages 726-730

  Milne, George W A ^a   Wang, Shaomeng ^a   Nicklaus, Marc C ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; FACTUAL DATABASE; HEALTH CARE ORGANIZATION; SYNTHESIS; UNITED STATES;

ANTINEOPLASTIC AGENTS; BINDING SITES; DATABASES, FACTUAL; DRUG DESIGN; MODELS, MOLECULAR; NATIONAL INSTITUTES OF HEALTH (U.S.); UNITED STATES;

EID: 0030191497     PISSN: 00952338     EISSN: None     Source Type: Journal    
DOI: 10.1021/ci9500849     Document Type: Article

References (30)

1. The starting for this effort is generally regarded as the authorization, in 1955 by the U.S. Congress of $5 million for the establishment by the NCI of a Drug Development Program. See: DeVita, V. T.; Oliverio, V. T.; Muggia, F. M.; Wiernik, P. W.; Ziegler, J.; Goldin, A.; Rubin, D.; Henney J.; Schepartz, S. The Drug Development and Clinical Trials Programs of the Division of Cancer Treatment, National Cancer Institute. Cancer Clin. Trials 1979, 2, 195-216.
2. In the NCI database, about half of the compounds are treated as proprietary ("discreet") upon request of the supplier. The remainder, together with all the data associated with them, are open to the public.
3. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
4. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
5. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
6. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
7. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
8. Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. I. System Overview. J. Chem. Inf. Comput. Sci. 1986, 26, 154-159. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS Pre-Registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168. Milne, G. W. A.; Feldman, A. P.; Miller, J. A.; Daly, G. P. The NCI Drug Information System. 3. The DIS Chemistry Module. J. Chem. Inf. Comput. Sci. 1986, 26, 168-179. Milne, G. W. A.; Miller, J. A.; Hoover, J. R. The NCI Drug Information System. 4. Inventory and Shipping Modules. J. Chem. Inf. Comput. Sci. 1986, 26, 179-185. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A. The NCI Drug Information System. 5. DIS Biology Module. J. Chem. Inf. Comput. Sci. 1986, 26, 186-193. Zehnacker, M. T.; Brennan, R. H.; Milne, G. W. A.; Miller, J. A.; Hammel M. J. The NCI Drug Information System. 6. System Maintenance. J. Chem. Inf. Comput. Sci. 1986, 26, 193-197.
9. Brint, A. T.; Willett, P. Pharmacophoric Pattern Matching in Files of 3D Chemical Structures: Comparison of Geometric Searching Algorithms. J. Mol. Graph. 1987, 5, 49-56.
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11. Wender, P. A.; Koehler, K. G.; Sharkey, N. A.; Dell'Aquila, M. L.; Blumberg, P. M. Analysis of the Phorbol Ester Pharmacophore on Protein Kinase C as a Guide to the Rational Design of New Classes of Analogs. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 4214-4218.
12. Nakamura, H.; Kishi, Y.; Pajares, M. A.; Rando, R. R. Structural Basis of Protein Kinase C Activation by Tumor Promoters. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 9672-9676.
13. See: Wang, S.; Milne, G. W. A.; Nicklaus, M. C.; Marquez, V. E.; Lee, J.; Blumberg, P. M. Protein Kinase C. Modeling of the Binding Site and Prediction of Binding Constants. J. Med. Chem. 1994, 37, 1326-1338 and references cited therein.
14. 6. Acta Crystallogr. 1971, B27, 1718-1730.
15. A program which attempts to characterize a pharmacophore from structure - activity data (Pharmacophore Identification in ChemDBS-3D) has been produced by Chemical Design Ltd., Roundway House, Cromwell Park, Chipping Norton, Oxon OX7 5SR U.K. Another such program, DISCO, was developed at Abbott Laboratories (Martin, Y. C.; Bures, M. G.; Danaher, E. A.; DeLazzer, J.; Lico, I.; Pavlik, P. A. A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists. J. Comput.-Aided Mol. Design 1993, 7, 83-102).
16. Miller, M.; Schneider, J.; Sathyanarayana, B. K.; Toth, M. V.; Marshall, G. R.; Clawson, L.; Selk, L.; Kent, S. B. H.; Wlodawer, A. Structure of a Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 Å Resolution. Science 1989, 246, 1149-1152.
17. Omichinski, J. G.; Trainor, C.; Evans, T.; Gronenborn, A. M.; Clore, G. M.; Felsenfeld, G. A Small Single-"Finger" Peptide from the Erythroid Transciption Factor GATA-1 Binds Specifically to DNA as a Zinc or Iron Complex. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 1676-1680.
18. Kazanietz, M. G.; Bustelo, X. R.; Barbacid, M.; Kolch, W.; Mischak, H.; Wong, G., Pettit, G. R.; Bruns, J. D.; Blumberg, P. M. Zing Finger Domains and Phorbol Ester Pharmacophore. J. Biol. Chem. 1994, 269, 11590-11594.
19. Milne, G. W. A.; Nicklaus, M. C.; Driscoll, J. S.; Wang, S.; Zaharevitz, D. National Cancer Institute Drug Information System 3D Database. J. Chem. Inf. Comput. Sci. 1994, 34, 1219-1224.
20. Hendrickson, M. A.; Nicklaus, M. C.; Milne, G. W. A. CONCORD and CAMBRIDGE: Comparison of Computer-Generated Chemical Structures with X-ray Crystallographic Data. J. Chem. Inf. Comput. Sci. 1993, 33, 155-163.
21. Nicklaus, M. C.; Milne, G. W. A.; Zaharevitz, D. Chem-X and CAMBRIDGE: Comparison of Computer-Generated Chemical Structures with X-Ray Crystallographic Data. J. Chem. Inf. Comput. Sci. 1993, 33, 639-646.
22. Chem-X is produced by Chemical Design Ltd., Roundway House, Cromwell Park, Chipping Norton, Oxon OX7 5SR U.K.
23. Sadowski, J.; Gasteiger, J.; Klebe, G. Comparison of Automatic Three-Dimensional Model Builders Using 639 X-ray Structures. J. Chem. Inf. Comput. Sci. 1994, 34, 1000-1008.
24. Wang, S.; Milne, G. W. A.; Nicklaus, M. C.; Marquez, V. E.; Lee, J.; Blumberg, P. M. Protein Kinase C: Modeling of the Binding Site and Prediction of Binding Constants. J. Med. Chem. 1994, 37, 1326-1338.
25. Wang, S.; Zaharevitz, D. W.; Sharma, R.; Marquez, V. E.; Lewin, N. E.; Du. L.; Blumberg, P. M.; Milne, G. W. A. The Discovery of Novel, Structurally Diverse Protein Kinase C Agonists Through Computer-3D Database Pharmacophore Search. Molecular Modeling Studies. J. Med. Chem. 1994, 37, 4479-4489.
26. Klopman, G.; Wang, S.; Balthasar, D. M. Estimation of Aqueous Solubility of Organic Molecules by the Group Contribution Approach. Application to the Study of Biodegradation. J. Chem. Inf. Comput. Sci. 1992, 32, 474-482.
27. Gillet, V. J.; Newell, W.; Mata, P.; Myatt, G.; Sike, S.; Zsoldos, Z.; Johnson, A. P. SPROUT: Recent Developments in the de novo Design of Molecules. J. Chem. Inf. Comput. Sci. 1994, 34, 207-217.
28. Hommel U.; Zurini, M. Solution Structure of a Cystein-Rich Domain of Rat Protein Kinase C. Nature Struct. Biol. 1994, 1, 383-387.
29. Kazanietz, M. G.; Wang, S.; Milne, G. W. A.; Lewin, N. E.; Liu, H. L.; Blumberg, P. M. Residues in the Seconf Cystein-Rich Region of PKCδ Relevant to Phorbol Ester Binding. J. Biol. Chem. 1995, 270, 14679-14684.
30. Wang, S.; Kazanietz, M. G.; Blumberg, P. M.; Marquez, V. E.; Milne, G. W. A. Molecular Modeling and Site-Directed Mutagenesis Studies of a Phorbol Ester Binding Site in Protein Kinase C. J. Med. Chem., in press.