Structural highlights
Publication Abstract from PubMed
Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered by surface plasmon resonance (SPR) screening of our in-house fragment library. Site specific binding of the primary hits was confirmed in a competition setup using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed the binding mode of 41 out of 48 selected fragment hits within the ATP-site. Structural comparison of the fragment binding modes with a DFG-out inhibitor of FAK initiated first synthetic follow-up optimization leading to improved binding affinity.
Fragment-based discovery of focal adhesion kinase inhibitors.,Gradler U, Bomke J, Musil D, Dresing V, Lehmann M, Holzemann G, Greiner H, Esdar C, Krier M, Heinrich T Bioorg Med Chem Lett. 2013 Oct 1;23(19):5401-9. doi: 10.1016/j.bmcl.2013.07.050. , Epub 2013 Jul 31. PMID:23973211[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gradler U, Bomke J, Musil D, Dresing V, Lehmann M, Holzemann G, Greiner H, Esdar C, Krier M, Heinrich T. Fragment-based discovery of focal adhesion kinase inhibitors. Bioorg Med Chem Lett. 2013 Oct 1;23(19):5401-9. doi: 10.1016/j.bmcl.2013.07.050. , Epub 2013 Jul 31. PMID:23973211 doi:10.1016/j.bmcl.2013.07.050
