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Publication Abstract from PubMed

Biophysical fragment screening of a thermostabilised beta1-adrenergic receptor (beta1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) phenyl piperazine hits 7 and 8. Subsequent hit to lead follow up confirmed the activity of the chemotype and a structure-based design approach using protein-ligand crystal structures of the beta1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilised beta1AR complexed with 19 and 20 were determined at resolutions of 2.8A and 2.7A, respectively.

Biophysical fragment screening of the beta1-adrenergic receptor: Identification of high affinity aryl piperazine leads using structure-based drug design.,Christopher J, Brown J, Dore A, Errey J, Koglin M, Marshall FH, Myszka D, Rich RL, Tate CG, Tehan B, Warne T, Congreve M J Med Chem. 2013 Mar 21. PMID:23517028^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.