Discovery and Nonclinical Development

  • Stephen F. Carroll

The discovery of new products for patient use takes place in laboratories at universities, in the government, or in pharmaceutical companies; actually, it starts in the minds of scientists with a scientific innovation or idea for creating a new therapeutic molecule that may be a biological or drug. This research is performed through carefully done studies, either with the physiology of humans or other species, disease models, or some core structure of a molecule, through a host of different scientific technologies. Sometimes, a drug discovery is an accidental finding related to an unexpected action of a drug being studied for other uses, such as Viagra® for impotence. Each molecule may have an impact on a general physiologic process such as inflammation and thus have the potential to be used in many organ systems and diseases, or it may impact a specific receptor on a cell, such as a tyrosine kinase, and be used only when the receptor system goes awry. Knowledge of the discovery and early development process creates a basis for understanding how potential new therapeutics advance from the research laboratory to the clinic and some of the issues involved.


Drug Discovery Biotech Company Drug Development Process Target Validation Target Discovery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
  2. 2.
    Gordon EJ, Myers KJ, Dougherty JP, Rosen H, Ron Y. Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol 1995;62(2):153–160.CrossRefPubMedGoogle Scholar
  3. 3.
    Werther WA, Gonzalez TN, O'Connor SJ, McCabe S, Chan B, Hotaling T, Champe M, Fox JA, Jardieu PM, Berman PW, Presta LG. Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1. J Immunol 1996;157(11):4986–4995.PubMedGoogle Scholar
  4. 4.
  5. 5.
    Myers S, Baker A. Drug discovery—an operating model for a new era. Nature Biotechnology 2001;19:727–730.CrossRefPubMedGoogle Scholar
  6. 6.
  7. 7.
    Roth BD. The discovery and development of atorvastatin, a potent novel hypolipidemic agent. Prog Med Chem 2002;40:1–22.CrossRefPubMedGoogle Scholar
  8. 8.
  9. 9.
    Winslow R. The birth of a blockbuster: lipitor's route out of the lab. New York Times. January 24, 2000.Google Scholar
  10. 10.
    Lieberman R. Evidence-based medical perspectives: the evolving role of PSA for early detection, monitoring of treatment response, and as a surrogate end point of efficacy for interventions in men with different clinical risk states for the prevention and progression of prostate cancer. Am J Ther 2004;11(6):501–506.CrossRefPubMedGoogle Scholar
  11. 11.
    Butcher EC, Berg EL, Kunkel EJ. Systems biology in drug discovery. Nat Biotechnol 2004 Oct;22(10):1253–1259.CrossRefPubMedGoogle Scholar
  12. 12.
    Lawrence CE. Acumen. J Sciences 2003;1:23.Google Scholar
  13. 13.
    Lindsay MA. Target discovery. Nat Rev Drug Discovery 2003; 2:831–838.CrossRefGoogle Scholar
  14. 14.
    Phizicky E, Bastiaens PI, Zhu H, Snyder M, Fields S. Protein analysis on a proteomic scale. Nature 2003;422(6928):208–215.CrossRefPubMedGoogle Scholar
  15. 15.
    Zambrowicz BP, Sands AT. Knockouts model the 100 best-selling drugs–will they model the next 100? Nat Rev Drug Discov 2003;2(1):38–51.CrossRefPubMedGoogle Scholar
  16. 16.
    Sachse C, Krausz E, Kronke A, Hannus M, Walsh A, Grabner A, Ovcharenko D, Dorris D, Trudel C, Sonnichsen B, Echeverri CJ. High-throughput RNA interference strategies for target discovery and validation by using synthetic short interfering RNAs: Functional genomics investigations of biological pathways. Methods Enzymol 2005;392:242–277.CrossRefPubMedGoogle Scholar
  17. 17.
    Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, Elbashir S, Geick A, Hadwiger P, Harborth J, John M, Kesavan V, Lavine G, Pandey RK, Racie T, Rajeev KG, Rohl I, Toudjarska I, Wang G, Wuschko S, Bumcrot D, Koteliansky V, Limmer S, Manoharan M, Vornlocher HP. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004;432(7014):173–178.CrossRefPubMedGoogle Scholar
  18. 18.
    Fougerolles A, Manoharan M, Meyers R, Vornlocher HP. RNA interference in vivo: Toward synthetic small inhibitory RNA-based therapeutics. Methods Enzymol 2005;392:278–296.CrossRefPubMedGoogle Scholar
  19. 19.
    Thomas FJ, McLeod HL, Watters JW. Pharmacogenomics: The influence of genomic variation on drug response. Curr Top Med Chem 2004;4(13):1399–1409.CrossRefPubMedGoogle Scholar
  20. 20.
    Harrington CA, Rosenow C, Retief J. Monitoring gene expression using DNA microarrays. Curr Opin Microbiol 2000;3(3): 285–291.CrossRefPubMedGoogle Scholar
  21. 21.
    MacBeath G, Schreiber SL. Printing proteins as microarrays for high-throughput function determination. Science 2000;289(5485): 1760–1763.PubMedGoogle Scholar
  22. 22.
    Yang Y, Blomme EA, Waring JF. Toxicogenomics in drug discovery: from preclinical studies to clinical trials. Chem Biol Interact 2004;150(1):71–85.CrossRefPubMedGoogle Scholar
  23. 23.
    Templin MF, Stoll D, Schwenk JM, Potz O, Kramer S, Joos TO. Protein microarrays: promising tools for proteomic research. Proteomics 2003;3(11):2155–2166.CrossRefPubMedGoogle Scholar
  24. 24.
  25. 25.
  26. 26.
    Griffiths AD. Production of human antibodies using bacteriophage. Curr Opin Immunol 1993;5(2):263–267.CrossRefPubMedGoogle Scholar
  27. 27.
    He M, Taussig MJ. Ribosome display: cell-free protein display technology. Brief Funct Genomic Proteomic 2002;1(2):204–212.CrossRefPubMedGoogle Scholar
  28. 28.
    Wernerus H, Stahl S. Biotechnological applications for surface-engineered bacteria. Biotechnol Appl Biochem 2004;40(Pt 3): 209–228.CrossRefPubMedGoogle Scholar
  29. 29.
    Verhoeyen M, Milstein C, Winter G. Reshaping human antibodies: grafting an antilysozyme activity. Science 1988;239(4847): 1534–1536.CrossRefPubMedGoogle Scholar
  30. 30.
  31. 31.
  32. 32.
    Bauer RJ, Dedrick RL, White ML, Murray MJ, Garovoy MR. Population pharmacokinetics and pharmacodynamics of the anti-CD11a antibody hu1124 in human subjects with psoriasis. J Pharmacokinet Biopharm 1999;27(4):397–420.CrossRefPubMedGoogle Scholar
  33. 33.
    Preziosi P. Science, pharmacoeconomics and ethics in drug R&D: a sustainable future scenario? Nat Rev Drug Discovery 2004;3(6):521–526.CrossRefGoogle Scholar
  34. 34.
  35. 35.
  36. 36.
  37. 37.
    Hodgson J. ADMET—turning chemicals into drugs. Nature Biotech 2001;19:722–726.CrossRefGoogle Scholar
  38. 38.
  39. 39.
    Carroll SF. Development partnerships—accelerating product development through collaborative programs. BioProc Intl 2003:48–53.Google Scholar
  40. 40.
    King J. Today's drug discovery: unlocking greater potential. R&D Directions 2004, 10(2):28–39.Google Scholar
  41. 41.
    Ernst & Young. Resurgence: Global Biotechnology Report 2004.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Stephen F. Carroll
    • 1
  1. 1.Altair BioConsultingWA

Personalised recommendations