Fragment-Based Drug Discovery

Traditional high-throughput screening has not delivered on its promise of increasing the numbers and quality of new drugs entering clinical trials. This lack of success is due in part to the complexity and the relatively large size of the compounds routinely being screened.

Astex is recognized as a leader in fragment-based drug discovery, one of the most significant advances in the last 20 years.

  • Starts with very small, low molecular weight drug fragments
  • These fragments have the potential to keep the overall complexity and molecular weight of each drug candidate low
  • These are key factors in successful drug development

Traditional bioassays used in high-throughput screening are generally unable to detect such small drug fragments because of their low potency binding to the protein target.

The Pyramid™ platform of Astex Pharmaceuticals™ integrates biophysical techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy and calorimetry, with fragment library design and a range of computational methodologies. This integration creates a proprietary approach for fragment-based drug discovery.

Due to the very high sensitivity of Pyramid™, fragment binding, not generally detectable using conventional screening techniques, can be routinely identified.

  • Affords a detailed understanding of the fragment’s binding environment at an atomic level
  • These structural insights support a very efficient chemistry optimization process in which each additional functional group is designed to contribute to protein binding in a defined and productive manner
  • Drug candidates are designed to have lower molecular weight, reduced metabolic liability, improved target selectivity and ease of chemical synthesis

Fragment Based Drug Screening

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AstexViewer

AstexViewer™ is a Java molecular graphics program that assists in structure-based drug design. OpenAstexViewer is freely available under an open source license from the following site: http://www.openastexviewer.net/web/.