title: [Strategy of molecular drug design: hits, leads and drug candidates].
abstract: Hits, leads and drug candidates constitute three millstones in the course of drug discovery and development. The definition of drug candidates is a critical point in the value chain of drug innovation, which not only differentiates the research and development stages, but more importantly, determines the perspective and destiny of the pre-clinical and clinical studies. All outcomes from the development stage are actually attributed to the chemical structure of candidates. The quality of candidates, however, is restricted by the drug-likeness of lead compounds, which in turn is decided by the characteristics of hits. The hit-to-lead is to provide a promising and druggable structure for further development, whereas the optimization of lead compounds is a process to transform an active compound into a drug, which in essence is molecular manipulation in multi-dimensional space related to pharmacodynamic, pharmacokinetic, physico-chemical, and safety properties. This review discusses the strategic principles in hit discovery, lead identification and optimization, as well as drug candidate definition with practical examples.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China. zrguo@imm.ac.cn
authors.forename: Zong-ru
authors.initials: ZR
authors.lastname: Guo
mesh_terms: D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004345:Drug Industry / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations