4JPA

Mmp13 in complex with a piperazine hydantoin ligand

Summary for 4JPA

• Entry DOI: 10.2210/pdb4jpa/pdb
• Related: 4JP4
• Descriptor: Collagenase 3, ZINC ION, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: matrix metalloprotease, calcium binding, zinc binding, hydrolase
• Biological source: Homo sapiens
• Cellular location: Secreted, extracellular space, extracellular matrix : P45452
• Total number of polymer chains: 2
• Total formula weight: 40430.34

Authors

Gerhardt, S.,Hargreaves, D. (deposition date: 2013-03-19, release date: 2014-03-05, Last modification date: 2024-03-20)

Primary citation

De Savi, C.,Waterson, D.,Pape, A.,Lamont, S.,Hadley, E.,Mills, M.,Page, K.M.,Bowyer, J.,Maciewicz, R.A.
Hydantoin based inhibitors of MMP13--discovery of AZD6605.
Bioorg.Med.Chem.Lett., 23:4705-4712, 2013

PubMed Abstract: Piperidine ether and aryl piperazine hydantoins are reported as potent inhibitors of MMP13. A medicinal chemistry campaign focused on replacing the reverse hydroxamate zinc binding group associated with historical inhibitors with a hydantoin zinc binding group then optimising MMP13 potency, solubility and DMPK properties whilst maintaining good selectivity over MMP14. A number of high quality candidates were progressed and following rat and dog safety evaluation, AZD6605 (3m) was identified as a candidate drug.

PubMed: 23810497
DOI: 10.1016/j.bmcl.2013.05.089

Experimental method

X-RAY DIFFRACTION (2 Å)