1YSG SAR by NMR ligands


FBDD is now an established methods of drug discovery having resulted in drugs delivered to patients and multiple compounds in clinical trials.  For groups without access to a compound collection or where the belief is that the target belongs to a class where you have few ligands, FBDD is a logical choice.  The key requirement is that you can access structural information to drive synthesis to make the small, weak ligands more potent.  FBDD has also provided a framework for people to think about what constitutes a good ligand via the debate round ligand efficiency, and how to improve potency.

The first paper to read is Hadjuk, Fesik et al’s “SAR by NMR”

“Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR”  J. Am. Chem. Soc., (1997), 119, 5818–5827

And then to follow up:

Murray & Rees,  Nature Chemistry (2009), 1,187–192

Congreve, et al, J. Med. Chem. (2008), 51, 3661–3680

And finally:

“Twenty years on: the impact of fragments on drug discovery”

Erlanson,  Fesik, Hubbard, Jahnke & Jhoti, Nature Reviews Drug Discovery (2016), 15 , 605-619


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