7A12
CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GW557358X (COMPOUND 9)
Summary for 7A12
| Entry DOI | 10.2210/pdb7a12/pdb |
| Descriptor | Methionine aminopeptidase 2, PHOSPHATE ION, 5-chloranyl-3-phenyl-1~{H}-indole-2-carboxamide, ... (5 entities in total) |
| Functional Keywords | methionine aminopeptidase-2, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42745.47 |
| Authors | Thorpe, J.H. (deposition date: 2020-08-11, release date: 2020-09-23, Last modification date: 2024-10-09) |
| Primary citation | Hirst, D.J.,Brandt, M.,Bruton, G.,Christodoulou, E.,Cutler, L.,Deeks, N.,Goodacre, J.D.,Jack, T.,Lindon, M.,Miah, A.,Page, K.,Parr, N.,Shukla, L.,Sims, M.,Thomas, P.,Thorpe, J.,Holmes, D.S. Structure-based optimisation of orally active & reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'. Bioorg.Med.Chem.Lett., 30:127533-127533, 2020 Cited by PubMed Abstract: Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physicochemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model. PubMed: 32919012DOI: 10.1016/j.bmcl.2020.127533 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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