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Trends in Modern Drug Discovery

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New Approaches to Drug Discovery

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 232))

Abstract

Drugs discovered by the pharmaceutical industry over the past 100 years have dramatically changed the practice of medicine and impacted on many aspects of our culture. For many years, drug discovery was a target- and mechanism-agnostic approach that was based on ethnobotanical knowledge often fueled by serendipity. With the advent of modern molecular biology methods and based on knowledge of the human genome, drug discovery has now largely changed into a hypothesis-driven target-based approach, a development which was paralleled by significant environmental changes in the pharmaceutical industry. Laboratories became increasingly computerized and automated, and geographically dispersed research sites are now more and more clustered into large centers to capture technological and biological synergies. Today, academia, the regulatory agencies, and the pharmaceutical industry all contribute to drug discovery, and, in order to translate the basic science into new medical treatments for unmet medical needs, pharmaceutical companies have to have a critical mass of excellent scientists working in many therapeutic fields, disciplines, and technologies. The imperative for the pharmaceutical industry to discover breakthrough medicines is matched by the increasing numbers of first-in-class drugs approved in recent years and reflects the impact of modern drug discovery approaches, technologies, and genomics.

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References

  • Algire GH, Chalkley HW (1945) Vascular reactions of normal and malignant tissues in vivo. 1. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6:73–85

    Google Scholar 

  • Arunlakshna O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Phamacol Chemother 14:48–58

    Article  Google Scholar 

  • Butenandt A (1931) Über die chemische Untersuchung der Sexualhormone. Angew Chem 46:905–908

    Article  Google Scholar 

  • Capdeville R, Buchdunger E, Zimmermann J et al (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1(7):493–502

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Morrow JK, Tran HT, Phatak SS, Du-Cuny L, Zhang S (2012) Curr Pharm Des 18:1217–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark AJ (1920) The effect of alterations of temperature upon functions of the isolated heart. J Physiol 54:275–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cortes R, Probst A, Palacios JM (1987) Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: forebrain. Neuroscience 20:65–107

    Article  CAS  PubMed  Google Scholar 

  • Cully M (2014) Trial watch: next-generation antimalarial from phenotypic screen shows clinical promise. Nat Rev Drug Discov 13(10):717

    Article  CAS  PubMed  Google Scholar 

  • Doudna JA, Charpentier E (2014) Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346(6213):1258096

    Article  PubMed  Google Scholar 

  • Eder J, Sedrani R, Wiesmann C (2014) The discovery of first-in-class drugs: origins and evolution. Nat Rev Drug Discov 13(8):577–587

    Article  CAS  PubMed  Google Scholar 

  • Falchi F, Caporuscio F, Recanatini M (2014) Structure-based design of small-molecule protein-protein interaction modulators: the story so far. Future Med Chem 6:343–357

    Article  CAS  PubMed  Google Scholar 

  • Fleming A (1929) On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Brit J Exp Path 10:226–236

    CAS  PubMed Central  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186

    Article  CAS  PubMed  Google Scholar 

  • Gao M, Nettles RE, Belema M et al (2010) Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465(7294):96–100

    Article  CAS  PubMed  Google Scholar 

  • Goodman LS, Gilman A (1975) The pharmacological basis of therapeutics, 5th edn. Macmillan, London, pp 27–32

    Google Scholar 

  • Greenblatt M, Shubi P (1968) Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41(1):111–124

    CAS  PubMed  Google Scholar 

  • Honigberg LA, Smith AM, Sirisawad M et al (2010) The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A 107(29):13075–13080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenakin TP (1987) Pharmacologic analysis of drug receptor interaction. Raven, New York

    Google Scholar 

  • Lahana R (1999) How many leads from HTS? Drug Disc Today 4:447–448

    Article  Google Scholar 

  • Langley JN (1880) On the antagonism of poisons. J Physiol 3:11–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langley JN (1905) On the reaction of cells and of nerve endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curare. J Physiol 33:374–413

    Article  PubMed  PubMed Central  Google Scholar 

  • Lefkowitz R, Roth J, Pricer W, Pastan I (1970) ACTH receptors in the adrenal: specific binding of ACTH-125I and its relation to adenyl cyclase. PNAS 65:745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309

    Article  CAS  PubMed  Google Scholar 

  • Linsley PS, Brady W, Urnes M et al (1991) CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 174(3):561–569

    Article  CAS  PubMed  Google Scholar 

  • Linsley PS, Greene JL, Tan P et al (1992) Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 176(6):1595–1604

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Pan S, Hsieh MH et al (2013) Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A 110(50):20224–20229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maibaum J, Feldman DL (2009) Case history on Tekturna/Rasilez (Aliskiren), a highly efficacious direct oral renin inhibitor as a new therapy for hypertension. Ann Rep Med Chem 44:105–127

    Article  CAS  Google Scholar 

  • Mohr SE, Smith JA, Shamu CE et al (2014) RNAi screening comes of age: improved techniques and complementary approaches. Nat Rev Mol Cell Biol 15(9):591–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mullard A (2014) 2013 FDA drug approvals. Nat Rev Drug Discov 13(2):85–89

    Article  PubMed  Google Scholar 

  • Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996

    Article  CAS  PubMed  Google Scholar 

  • Perzborn E, Roehrig S, Straub A, Kubitza D, Misselwitz F (2011) The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nat Rev Drug Discov 10(1):61–75

    Article  CAS  PubMed  Google Scholar 

  • Presta LG, Chen H, O’Connor SJ et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57(20):4593–4599

    CAS  PubMed  Google Scholar 

  • Quintás-Cardama A, Vaddi K, Liu P et al (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 115(15):3109–3117

    Article  PubMed  PubMed Central  Google Scholar 

  • Rottmann M, McNamara C, Yeung BK et al (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science 329(5996):1175–1180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sala E, Mologni L, Truffa S et al (2008) BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res 6(5):751–759

    Article  CAS  PubMed  Google Scholar 

  • Scannell JW, Blanckley A, Boldon H et al (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 11(3):191–200

    Article  CAS  PubMed  Google Scholar 

  • Schrör K (2008) Acetylsalicylic acid. Wiley-Blackwell, London

    Book  Google Scholar 

  • Schulze U, Ringel M (2013) What matters most in commercial success: first-in-class or best-in-class? Nat Rev Drug Discov 12(6):419–420

    Article  CAS  PubMed  Google Scholar 

  • Shtivelman E, Lifshitz B, Gale RP et al (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315(6020):550–554

    Article  CAS  PubMed  Google Scholar 

  • Tobert JA (2003) Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov 2(7):517–526

    Article  CAS  PubMed  Google Scholar 

  • Torphy TJ, Undem BJ (1991) Phosphodiesterase inhibitors: new opportunities for the treatment of asthma. Thorax 46(7):512–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsai J, Lee JT, Wang W et al (2008) Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A 105(8):3041–3046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward WH, Cook PN, Slater AM et al (1994) Epidermal growth factor receptor tyrosine kinase. Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor. Biochem Pharmacol 48(4):659–666

    Article  CAS  PubMed  Google Scholar 

  • Wholley D (2014) The biomarkers consortium. Nat Rev Drug Disc Today 13:791–792

    Article  CAS  Google Scholar 

  • Woakes E (1868) On Ergot of Rye in the treatment of Neuralgia. Br Med J 2(405):360–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Novartis Pharma AG, CH-4056, Basel, Switzerland

    Jörg Eder & Paul L. Herrling

Authors
  1. Jörg Eder
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  2. Paul L. Herrling
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Corresponding author

Correspondence to Paul L. Herrling .

Editor information

Editors and Affiliations

  1. Drug Discovery-Cross Indication Platform, Bayer Pharma AG, Wuppertal, Germany

    Ulrich Nielsch

  2. Drug Discovery-Cross Indication Platform, Bayer Pharma AG, Berlin, Berlin, Germany

    Ulrike Fuhrmann

  3. Drug Discovery-Global External Innovation & Alliances, Bayer Pharma AG, Berlin, Berlin, Germany

    Stefan Jaroch

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© 2015 Springer International Publishing Switzerland

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Eder, J., Herrling, P.L. (2015). Trends in Modern Drug Discovery. In: Nielsch, U., Fuhrmann, U., Jaroch, S. (eds) New Approaches to Drug Discovery. Handbook of Experimental Pharmacology, vol 232. Springer, Cham. https://doi.org/10.1007/164_2015_20

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