8K5X
Crystal structure of human proMMP-9 catalytic domain in complex with inhibitor
Summary for 8K5X
| Entry DOI | 10.2210/pdb8k5x/pdb |
| Descriptor | Matrix metalloproteinase-9, ZINC ION, CALCIUM ION, ... (7 entities in total) |
| Functional Keywords | mmp-9, 92 kda gelatinase, 92 kda type iv collagenase, gelatinase b, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 55648.40 |
| Authors | |
| Primary citation | Nishikawa-Shimono, R.,Kuwabara, M.,Fujisaki, S.,Matsuda, D.,Endo, M.,Kamitani, M.,Futamura, A.,Nomura, Y.,Yamaguchi-Sasaki, T.,Yabuuchi, T.,Yamaguchi, C.,Tanaka-Yamamoto, N.,Satake, S.,Abe-Sato, K.,Funayama, K.,Sakata, M.,Takahashi, S.,Hirano, K.,Fukunaga, T.,Uozumi, Y.,Kato, S.,Tamura, Y.,Nakamori, T.,Mima, M.,Mishima-Tsumagari, C.,Nozawa, D.,Imai, Y.,Asami, T. Discovery of novel indole derivatives as potent and selective inhibitors of proMMP-9 activation. Bioorg.Med.Chem.Lett., 97:129541-129541, 2023 Cited by PubMed Abstract: Matrix metalloproteinase-9 (MMP-9) is a secreted zinc-dependent endopeptidase that degrades the extracellular matrix and basement membrane of neurons, and then contributes to synaptic plasticity by remodeling the extracellular matrix. Inhibition of MMP-9 activity has therapeutic potential for neurodegenerative diseases such as fragile X syndrome. This paper reports the molecular design, synthesis, and in vitro studies of novel indole derivatives as inhibitors of proMMP-9 activation. High-throughput screening (HTS) of our internal compound library and subsequent merging of hit compounds 1 and 2 provided compound 4 as a bona-fide lead. X-ray structure-based design and subsequent lead optimization led to the discovery of compound 33, a highly potent and selective inhibitor of proMMP-9 activation. PubMed: 37952596DOI: 10.1016/j.bmcl.2023.129541 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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