4C3F
Structure of Lck in complex with a compound discovered by Virtual Fragment Linking
Summary for 4C3F
| Entry DOI | 10.2210/pdb4c3f/pdb |
| Descriptor | TYROSINE-PROTEIN KINASE LCK, N-phenyl-4-(5-phenyl-1H-pyrazol-4-yl)pyrimidin-2-amine (3 entities in total) |
| Functional Keywords | transferase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 30969.51 |
| Authors | Cowan-Jacob, S.W.,Rummel, G.,Stark, W. (deposition date: 2013-08-23, release date: 2013-10-23, Last modification date: 2023-12-20) |
| Primary citation | Wassermann, A.M.,Kutchukian, P.S.,Lounkine, E.,Luethi, T.,Hamon, J.,Bocker, M.T.,Malik, H.A.,Cowan-Jacob, S.W.,Glick, M. Efficient search of chemical space: navigating from fragments to structurally diverse chemotypes. J. Med. Chem., 56:8879-8891, 2013 Cited by PubMed Abstract: We introduce a novel strategy to sample bioactive chemical space, which follows-up on hits from fragment campaigns without the need for a crystal structure. Our results strongly suggest that screening a few hundred or thousand fragments can substantially improve the selection of small-molecule screening subsets. By combining fragment-based screening with virtual fragment linking and HTS fingerprints, we have developed an effective strategy not only to expand from low-affinity hits to potent compounds but also to hop in chemical space to substantially novel chemotypes. In benchmark calculations, our approach accessed subsets of compounds that were substantially enriched in chemically diverse hit compounds for various activity classes. Overall, half of the hits in the screening collection were found by screening only 10% of the library. Furthermore, a prospective application led to the discovery of two structurally novel histone deacetylase 4 inhibitors. PubMed: 24117015DOI: 10.1021/jm401309q PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.72 Å) |
Structure validation
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