Fragment-based lead discovery

Fragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. Fragments are small organic molecules which are small in size and low in molecular weight.[1] It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity. FBLD can be compared with high-throughput screening (HTS). In HTS, libraries with up to millions of compounds, with molecular weights of around 500 Da, are screened, and nanomolar binding affinities are sought. In contrast, in the early phase of FBLD, libraries with a few thousand compounds with molecular weights of around 200 Da may be screened, and millimolar affinities can be considered useful.[2] FBLD is a technique being used in research for discovering novel potent inhibitors.[1] This methodology could help to design multitarget drugs for multiple diseases. The multitarget inhibitor approach is based on designing an inhibitor for the multiple targets. This type of drug design opens up new polypharmacological avenues for discovering innovative and effective therapies. Neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s, among others, also show rather complex etiopathologies. Multitarget inhibitors are more appropriate for addressing the complexity of AD and may provide new drugs for controlling the multifactorial nature of AD, stopping its progression. [3]

  1. ^ a b Price AJ, Howard S, Cons BD (November 2017). "Fragment-based drug discovery and its application to challenging drug targets". Essays in Biochemistry. 61 (5): 475–484. doi:10.1042/EBC20170029. PMID 29118094.
  2. ^ Tounge BA, Parker MH (2011). "Designing a Diverse High-Quality Library for Crystallography-Based FBDD Screening". Fragment-Based Drug Design - Tools, Practical Approaches, and Examples. Methods in Enzymology. Vol. 493. pp. 3–20. doi:10.1016/B978-0-12-381274-2.00001-7. ISBN 9780123812742. PMID 21371585.
  3. ^ Gharaghani S, Khayamian T, Ebrahimi M (October 2013). "Multitarget fragment-based design of novel inhibitors for AChE and SSAO/VAP-1 enzymes". Journal of Chemometrics. 27 (10): 297–305. doi:10.1002/cem.2556. S2CID 86409773.