Antimycotic drug discovery in the age of genomics.
Genomic-based methodologies are increasingly used at all stages of drug development. The most extensive applications have occurred in early drug discovery stages due to advances in technologies that allow for automated synthesis and characterization of organic compounds, and for high-throughput screening of these molecules against known drug targets. The adaptation of genomic-based methodologies in later stages of drug development presents a more difficult task. In this review we describe how genomics can be used to identify previously uncharacterized pharmacologic actions that provide a basis for the development of new classes of antimycotic agents or for adverse event aversion. Clinically, novel antimycotics are gravely needed. This review provides a perspective on new technologies that will bridge the gap between drug discovery and development that may enable more rapid access to new antimycotic agents.
Cleary
John D
JD
Department of Pharmacy Practice & Medicine, University of Mississippi, Jackson, Mississippi 39216, USA. jcleary@medicine.umsmed.edu
Walker
Larry A
LA
Hawke
Roy L
RL
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005658:Fungi / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D020869:Gene Expression Profiling / Q000379:methods; D016681:Genome, Fungal / Q000187:drug effects; D023281:Genomics / Q000379:methods; D006632:Histamine / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013379:Substrate Specificity
D000935:Antifungal Agents; D026901:Membrane Transport Proteins; D006632:Histamine; D003577:Cytochrome P-450 Enzyme System