From fragment to clinical candidate--a historical perspective.
As recently as ten years ago few scientists had heard of fragment screening, let alone considered low molecular weight fragments (MW <300) with weak binding affinities to be attractive start points for drug discovery programmes. Today, however, there is widespread acceptance that these fragments can be progressed into lead series and on to become clinical candidates. Consequently, over the past three to four years, fragment-based drug discovery has become firmly established within the biotechnology and pharmaceutical industries as a complimentary strategy to high-throughput screening. In this review, we give a historical perspective of how rapidly fragment-based drug discovery has developed and describe a number of clinical compounds discovered using this approach.
Chessari
Gianni
G
Astex Therapeutics Ltd., 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK.
Woodhead
Andrew J
AJ
D000818:Animals; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods* / Q000639:trends*; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000639:trends; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry / Q000627:therapeutic use; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*
D010446:Peptide Fragments; D047492:Peroxisome Proliferator-Activated Receptors; D004364:Pharmaceutical Preparations; D051357:Cyclin-Dependent Kinase 2