title: Quality by design in lead optimization: a new strategy to address productivity in drug discovery.
abstract: The constant decline in drug discovery productivity despite the continuous growth in R&D investments has been on the table for many years and is driving changes in the current business model. We have focused our attention on what appears to be by far the major cause of attrition, the intrinsic quality of drug candidates; with the assumption that candidate quality can be designed and assessed at a rather early stage in drug discovery we have developed tools such as CNS chemical space mapping through PLS analysis, Drug Efficiency (DRUG(eff)) and the mechanistic PK/PD hypothesis. We also introduced best practices that were found extremely valuable which will be discussed in this article.
authors.affiliation: Aptuit Medicines Research Centre, Via Fleming 4, Verona, Italy. tino.rossi@aptuit.com
authors.forename: Tino
authors.initials: T
authors.lastname: Rossi
authors.forename: Simone
authors.initials: S
authors.lastname: Braggio
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D003627:Data Interpretation, Statistical; D055808:Drug Discovery / Q000379:methods*; D004345:Drug Industry / Q000458:organization & administration; D017598:Efficiency, Organizational; D006801:Humans
chemical_list: D002491:Central Nervous System Agents