PUBLICATION

Multi-step usage of in vivo models during rational drug design and discovery

Authors
Williams, C.H., and Hong, C.C.
ID
ZDB-PUB-110713-32
Date
2011
Source
International Journal of Molecular Sciences   12(4): 2262-2274 (Journal)
Registered Authors
Hong, Charles
Keywords
pheotypic screen, drug discovery, small molecules, drug design chemical genetics, model organisms
MeSH Terms
  • Animals
  • Drug Design*
  • Drug Discovery
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Models, Animal*
  • Pharmaceutical Preparations/metabolism*
  • Structure-Activity Relationship
PubMed
21731440 Full text @ Int. J. Mol. Sci.
Abstract
In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping