Discovery of novel drugs for promising targets.
BACKGROUND
Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging.


OBJECTIVE
The goal of this study was to provide a road map to navigate drug discovery.


METHODS
Review general steps for drug discovery and provide illustrating references.


RESULTS
A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed.


CONCLUSIONS
Drug discovery is a complex process that has significantly evolved in recent years.
TESARO Inc, Waltham, Massachusetts; Tufts Medical Center, Boston, Massachusetts. Electronic address: rmartell@tesarobio.com.
Robert E
RE
Martell
David G
DG
Brooks
Yan
Y
Wang
Keith
K
Wilcoxen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D019295:Computational Biology; D004195:Disease Models, Animal; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D015507:Drugs, Investigational / Q000494:pharmacology* / Q000627:therapeutic use; D057166:High-Throughput Screening Assays; D006801:Humans; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D015513:Oncogene Proteins
cancer; drug discovery