3KRY

Crystal structure of MMP-13 in complex with SC-78080

Summary for 3KRY

• Entry DOI: 10.2210/pdb3kry/pdb
• Related: 1HFC 966C
• Descriptor: Collagenase 3, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: collagenase, collagenase-3, mmp-13, collagen degradation, disease mutation, disulfide bond, extracellular matrix, glycoprotein, hydrolase, metal-binding, metalloprotease, protease, secreted
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P45452
• Total number of polymer chains: 4
• Total formula weight: 76952.67

Authors

Kiefer, J.R.,Williams, J.M.,Becker, D.P. (deposition date: 2009-11-19, release date: 2010-10-06, Last modification date: 2024-02-21)

Primary citation

Becker, D.P.,Barta, T.E.,Bedell, L.J.,Boehm, T.L.,Bond, B.R.,Carroll, J.,Carron, C.P.,Decrescenzo, G.A.,Easton, A.M.,Freskos, J.N.,Funckes-Shippy, C.L.,Heron, M.,Hockerman, S.,Howard, C.P.,Kiefer, J.R.,Li, M.H.,Mathis, K.J.,McDonald, J.J.,Mehta, P.P.,Munie, G.E.,Sunyer, T.,Swearingen, C.A.,Villamil, C.I.,Welsch, D.,Williams, J.M.,Yu, Y.,Yao, J.
Orally-active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease
J.Med.Chem., 53:6653-6680, 2010

PubMed Abstract: α-Sulfone-α-piperidine and α-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. α-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while α-piperidine and α-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.

PubMed: 20726512
DOI: 10.1021/jm100669j

Experimental method

X-RAY DIFFRACTION (1.9 Å)