3N4C

6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors

Summary for 3N4C

• Entry DOI: 10.2210/pdb3n4c/pdb
• Descriptor: Cathepsin S, (E)-1-(1-methyl-6-{4-[3-(4-methylpiperazin-1-yl)propoxy]-3-(trifluoromethyl)phenyl}-1H-imidazo[4,5-c]pyridin-4-yl)methanimine, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: cathepsin s, covalent inhibitor, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P25774
• Total number of polymer chains: 2
• Total formula weight: 49187.19

Authors

Fradera, X.,Uitdehaag, J.C.M.,van Zeeland, M. (deposition date: 2010-05-21, release date: 2011-04-06, Last modification date: 2024-11-06)

Primary citation

Cai, J.,Baugh, M.,Black, D.,Long, C.,Jonathan Bennett, D.,Dempster, M.,Fradera, X.,Gillespie, J.,Andrews, F.,Boucharens, S.,Bruin, J.,Cameron, K.S.,Cumming, I.,Hamilton, W.,Jones, P.S.,Kaptein, A.,Kinghorn, E.,Maidment, M.,Martin, I.,Mitchell, A.,Rankovic, Z.,Robinson, J.,Scullion, P.,Uitdehaag, J.C.,Vink, P.,Westwood, P.,van Zeeland, M.,van Berkom, L.,Bastiani, M.,Meulemans, T.
6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors.
Bioorg.Med.Chem.Lett., 20:4350-4354, 2010

PubMed Abstract: 6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays.

PubMed: 20598883
DOI: 10.1016/j.bmcl.2010.06.072

Experimental method

X-RAY DIFFRACTION (1.9 Å)