The heart of drug discovery and development: Rational target selection

Pharmacology

Volumn 77, Issue 2, 2006, Pages 85-92

  Spector, Reynold ^a,b   Vesell, Elliot S ^c  

^a ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Allopurinol; Drug target selection; Pathophysiology; Statins; Vaccine and drug discovery

Indexed keywords

ALENDRONIC ACID; ALLOPURINOL; ALPHA TOCOPHEROL; ANTIHYPERTENSIVE AGENT; BISPHOSPHONIC ACID DERIVATIVE; CALCIUM; CHOLECYSTOKININ RECEPTOR BLOCKING AGENT; DENOSUMAB; DUTASTERIDE; ESTROGEN; FIBRIC ACID DERIVATIVE; FINASTERIDE; HYDRALAZINE; HYDROCHLOROTHIAZIDE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IBANDRONIC ACID; MONOCLONAL ANTIBODY; ORPHAN DRUG; RESERPINE; RESIN; RISEDRONIC ACID; STEROID 5ALPHA REDUCTASE INHIBITOR; TRIPARANOL; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANIMAL MODEL; ARTICLE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DISEASE CONTROL; DISEASE MARKER; DISEASE MODEL; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGET SELECTION; DRUG TARGETING; EPIDEMIOLOGY; GASTROINTESTINAL DISEASE; GENE TARGETING; GENOMICS; GOUT; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTENSION; INFLUENZA; MOLECULAR BIOLOGY; MOLECULAR TARGETING; NONHUMAN; OBSERVATIONAL STUDY; OSTEOPOROSIS; PATHOPHYSIOLOGY; PREVENTIVE MEDICINE; PRIORITY JOURNAL; SIDE EFFECT; VACCINE PRODUCTION;

ANIMALS; ANTIBODIES, MONOCLONAL; BONE DENSITY CONSERVATION AGENTS; CHOLECYSTOKININ; DIPHOSPHONATES; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; EPIDEMIOLOGIC STUDIES; ESTROGEN REPLACEMENT THERAPY; GENOMICS; HUMANS; OSTEOPOROSIS;

EID: 33744793736     PISSN: 00317012     EISSN: None     Source Type: Journal    
DOI: 10.1159/000093166     Document Type: Article

References (40)

1. Spector R: Progress in the search for ideal drugs. Pharmacology 2002;64:1-7.
2. Spector R, Vesell ES: The pursuit of truth: role of epidemiology/ observation studies. J Clin Pharmacol 2000;40:1205-1210.
3. Spector R, Vesell ES: Which studies of therapy merit credence? Vitamin E and estrogen as cautionary examples. J Clin Pharmacol 2002;42:955-962.
4. Spector R, Vesell ES: A rational approach to the selection of drugs for clinical practice. Pharmacology 2002;65:57-61.
5. Spector R, Vesell ES: The power of pharmacological sciences: the example of the proton pump inhibitors. Pharmacology 2006;76:148-156.
6. Rebec GV, Barton SJ, Ennis MD: Dysregulation of ascorbate release in striatum of behaving mice expressing the Huntington's disease gene. J Neurosci 2002;22:RC202.
7. Vagelos R, Galambos L: Medicine, Science and Merck. Cambridge, Cambridge University Press, 2004.
8. Rundles RW, Wyngaarden JB, Hitchings GH, Elion GB: Drugs and uric acid. Ann Rev Pharmacol 1969;9:345-362.
9. 2-receptors. Nature 1972;236:385-390.
10. Enomoto A, Kimura H, Chairoungdua A, et al: Molecular identification of a renal urate-anion exchanger that regulates blood urate levels. Nature 2002;417:447-451.
11. Ichioka K, Hosoyamada M, Hisatome I, et al: Clinical and molecular analysis of patients with renal hypouricemia in Japan - influence of URAT-1 gene on urinary urate excretion. J Am Soc Nephrol 2004;15:164-173.
12. Veterans Administration Cooperative Study Group: Effects of treatment on morbidity in hypertension. JAMA 1967;202:1028-1034.
13. Spector R: The Scientific Basis of Clinical Pharmacology: Principles and Examples. Boston, Little Brown, 1986.
14. Jackson EK: Renin and angiotension; in Brunton LL (ed): Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York, McGraw-Hill, 2006, pp 789-821.
15. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvistatin Survival Study (4S). Lancet 1994;344:1383-1389.
16. Baigent C, Keech A, Kearney PM, et al, Cholesterol Treatment Trialists' (CTT) Collaborators: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis from 90,056 participants in 14 randomized trials of statins. Lancet 2005;366:1267-1278.
17. Opie LH: Controversies in cardiology. Lancet 2006;367:13-14.
18. Spake D: The menopausal marketplace. US News World Rep 2002;133:42-50.
19. Cauley JA, Robkins J, Chen Z, et al: Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003;290:1729-1738.
20. Raisz LG: Pathogenesis of osteoporosis: concepts, conflicts and prospects. J Clin Invest 2005;115:3318-3325.
21. McClung MR, Lewiecki EM, Cohen SB, et al, AMG 162 Bone Loss Study Group: Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821-831.
22. Liddle R, Gertz BJ, Kansyama S: Effect of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK. J Clin Invest 1989;84:1220-1225.
23. Anderson GL, Limacher M, Assaf AR, et al, Women's Health Initiative Steering Committee: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;29:1701-1712.
24. Brown BG, Crowley J: Is there any hope for vitamin E. JAMA 2005;293:1387-1390.
25. Howard BV, Van Horn L, Hsia J, et al: Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:655-666.
26. Beresford SAA, Johnson KL, Ritenbaugh C, et al: Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:643-654.
27. Prentice RL, Cann B, Chlebowski RW, et al: Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:629-642.
28. Jackson RD, LaCroix AZ, Gass M, et al, Women's Health Initiative Investigators: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-683.
29. Wactawski-Wende J, Kotchen JM, Anderson GL, et al, Women's Health Initiative Investigators: Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684-696.
30. Davey Smith G, Ebrahim S: Folate supplementation and cardiovascular disease. Lancet 2005;366:1679-1681.
31. Bonaa KH, Njolstad I, Ueland PM, et al: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-1588.
32. Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators: Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-1577.
33. Col NF, Pauker SG: The discrepancy between observational and randomized trials of menopausal hormone therapy: did expectations shape experience? Ann Intern Med 2003;139:923-929.
34. Ioannidis JPA: Contradicted and initially stronger effects in highly cited clinical research. JAMA 2005;294:218-228.
35. Sempos CT: Some limitations of semiquantitative food frequency questionnaires. Am J Epidemiol 1992;135:1127-1132.
36. Grodstein F, Manson JE, Stampfer M: Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt) 2006;15:35-44.
37. Hsia J, Langer RD, Manson JE: Conjugated equine estrogens and coronary heart disease. Arch Intern Med 2006;166:357-365.
38. Editorial: Low-fat diets flub a test. NY Times 2006;Feb 9:A26.
39. McConnell JD, Bruskewitz R, Walsh P, et al: The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med 1998;338:557-563.
40. Roehrborn CG, Marks LS, Fenter T, et al: Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 2004;63:709-715.