Drug Efficacy, Safety, and Biologics Discovery: Emerging by Sean Ekins

By Sean Ekins

This publication covers key rising applied sciences - specific less than in regards to the subject - in pharmaceutical R & D and the way they've got considerably impacted (or are presently impacting) drug discovery. The cross-disciplinary collaborations implicit in integrating those applied sciences with drug discovery operations will gas the engine for destiny recommendations. This publication cuts around the a number of components of drug discovery, every one bankruptcy authored via pioneers in that box, making for a large attract the chemical and organic scientists and technologists curious about drug discovery and improvement.

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Sample text

In the current drug discovery paradigm, initial lead compounds are often identified from in vitro highthroughput screens (HTS), for example, an inhibition assay against a target enzyme or receptor. , EC50). When such a correlation does not exist, there is added uncertainty as to the validity of the pharmacological target and/or the in vitro screening strategy. Also the HTS cannot be relied upon to drive the structure activity relationship (SAR), and quantitative predictions of TI become impossible to derive.

6. Giacomini KM, Roden KR, Eichelbaum DM, Hayden MR, Nakamura Y. When good drugs go bad. Nature 2007;446:975–7. 7. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 2004;3:711–6. 8. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007;356:1304–16. 9. Schuster D, Laggner C, Langer T. Why drugs fail—a study on side effects in new chemical entities.

1). It is now widely recognized that drug toxicity is the leading cause of drug candidate attrition in development [5], as well as drug withdrawals Traditional Discovery and Development Target Screen Lead HTS: Potency Animal: Potency ADME, hERG,GenTox, Selectivity Candidate Pre-clinical Clinical In vivo Safety TI good Studies: preclinical and clinical Lack of TI GO STOP Q: Why not screen against the end goal: therapeutic index (TI)? 1 Role of therapeutic index (TI) screening in drug discovery and development.

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