title: Therapeutic targets: progress of their exploration and investigation of their characteristics.
abstract: Modern drug discovery is primarily based on the search and subsequent testing of drug candidates acting on a preselected therapeutic target. Progress in genomics, protein structure, proteomics, and disease mechanisms has led to a growing interest in and effort for finding new targets and more effective exploration of existing targets. The number of reported targets of marketed and investigational drugs has significantly increased in the past 8 years. There are 1535 targets collected in the therapeutic target database compared with approximately 500 targets reported in a 1996 review. Knowledge of these targets is helpful for molecular dissection of the mechanism of action of drugs and for predicting features that guide new drug design and the search for new targets. This article summarizes the progress of target exploration and investigates the characteristics of the currently explored targets to analyze their sequence, structure, family representation, pathway association, tissue distribution, and genome location features for finding clues useful for searching for new targets. Possible "rules" to guide the search for druggable proteins and the feasibility of using a statistical learning method for predicting druggable proteins directly from their sequences are discussed.
authors.affiliation: Bioinformatics and Drug Design Group, Department of Computational Science, National University of Singapore, Singapore, Singapore.
authors.forename: C J
authors.initials: CJ
authors.lastname: Zheng
authors.forename: L Y
authors.initials: LY
authors.lastname: Han
authors.forename: C W
authors.initials: CW
authors.lastname: Yap
authors.forename: Z L
authors.initials: ZL
authors.lastname: Ji
authors.forename: Z W
authors.initials: ZW
authors.lastname: Cao
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001665:Binding Sites; D030562:Databases, Protein; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011487:Protein Conformation; D017510:Protein Folding; D040901:Proteomics; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011943:Receptors, Adrenergic, beta; D020782:Matrix Metalloproteinases