Fragment-Based Drug Discovery

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In recent years, Fragment-Based Drug Discovery (FBDD) has become a powerful approach to identify novel drug candidates. With over 20 molecules in clinical trials and one FDA-approved drug (vemurafenib) derived from FBDD, this approach has gained considerable popularity amongst the pharmaceutical/biotech industry.

FBDD relies on the identification of low molecular weight compounds called fragments (MW< 300) that often bind weakly to a biological target. The fragments can then be evolved by various methods (growing, linking, merging, remodeling) to achieve the desired biological activity and drug-like properties.

Fragment-Based Drug Discovery
Advantages of FBDD

  • Fragment libraries offer a better coverage of the chemical space.
  • Optimization of a fragment hit is more likely to produce molecules with drug-like properties.
  • Fragment hits have generally high ligand efficiency (LE = -ΔG/# non-H atoms).
  • Molecules derived from fragment hits usually require a smaller number of synthetic steps.

At Aunova Medchem, we are expert in converting low affinity fragment hits into potent chemical leads. We can efficiently support your medicinal chemistry projects and deliver to you high quality chemical leads to advance your projects. We have experience working with different biological target classes including kinases, G-protein coupled receptors (GPCR) and Protein-Protein interactions (PPI).  See below our list of services.

Services

  • Assembly of fragment library
  • Fragment hits assessment/validation: SAR by catalogue
  • Fragment hits optimization: Generation of small focused libraries and/or singletons
  • Collaborative structure-based design
  • Lead optimization

References

  1.  Introduction to fragment-based drug discovery. Erlanson, D.A. Topics in Current Chemistry 2012, 317, 1-32.
  2. Fragment-based approaches in drug discovery and chemical biology. Scott, D.; Coyne, A.; Hudson, S.; Abell, C. Biochemistry 2012, 51, 4990-5003.
  3. Vemurafenib: the first drug approved for BRAF-mutant cancer. Bollag, G.; Tsai, J.; Zhang, J.; Zhang, C.; Ibrahim, P.; Nolop, K.; Hirth, P. Nature Reviews. Drug Discovery 2012, 11, 873-886.
  4. The rise of fragment-based drug discovery. Murray, C.W.; Rees, D.C. Nature Chemistry 2009, 1, 187-192.