title: Advances in fragment-based drug discovery platforms.
abstract: BACKGROUND
  Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique.
  
  
  OBJECTIVE
  Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique.
  
  
  CONCLUSIONS
  Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka Tsukuba, Ibaraki 305-8585, Japan +81 29 863 6768 ; +81 29 856 2558 ; masaya.orita@jp.astellas.com.
authors.forename: Masaya
authors.initials: M
authors.lastname: Orita
authors.forename: Masaichi
authors.initials: M
authors.lastname: Warizaya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Amano
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ohno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Niimi