Discovery of novel drugs for promising targets

Clin Ther. 2013 Sep;35(9):1271-81. doi: 10.1016/j.clinthera.2013.08.005.

Abstract

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.

Keywords: cancer; drug discovery.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Line, Tumor
  • Computational Biology
  • Disease Models, Animal
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Drugs, Investigational / pharmacology*
  • Drugs, Investigational / therapeutic use
  • High-Throughput Screening Assays
  • Humans
  • Molecular Docking Simulation
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Reproducibility of Results
  • United States
  • United States Food and Drug Administration

Substances

  • Antineoplastic Agents
  • Drugs, Investigational
  • Oncogene Proteins