Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K

被引：67

作者：

Altmann, E ^{[1
]}

Cowan-Jacob, SW ^{[1
]}

Missbach, M ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 24期

关键词：

D O I：

10.1021/jm0493111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from the high-throughput screening hit la, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.

引用

收藏

页码：5833 / 5836

页数：4

相关论文

共 17 条

[1] Proteolytic activity of human osteoclast cathepsin K - Expression, purification, activation, and substrate identification [J].

Bossard, MJ ;

Tomaszek, TA ;

Thompson, SK ;

Amegadzie, BY ;

Hanning, CR ;

Jones, C ;

Kurdyla, JT ;

McNulty, DE ;

Drake, FH ;

Gowen, M ;

Levy, MA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) :12517-12524

[2]

Deaton DN, 2004, PROGR MED CHEM, V42, P245, DOI 10.1016/S0079-6468(04)42006-2

[3] Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts [J].

Drake, FH ;

Dodds, RA ;

James, IE ;

Connor, JR ;

Debouck, C ;

Richardson, S ;

LeeRykaczewski, E ;

Coleman, L ;

Rieman, D ;

Barthlow, R ;

Hastings, G ;

Gowen, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) :12511-12516

[4] The collagenolytic activity of cathepsin K is unique among mammalian proteinases [J].

Garnero, P ;

Borel, O ;

Byrjalsen, I ;

Ferreras, M ;

Drake, FH ;

McQueney, MS ;

Foged, NT ;

Delmas, PD ;

Delaissé, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (48) :32347-32352

[5] LINKAGE OF PYCNODYSOSTOSIS TO CHROMOSOME 1Q21 BY HOMOZYGOSITY MAPPING [J].

GELB, BD ;

EDELSON, JG ;

DESNICK, RJ .

NATURE GENETICS, 1995, 10 (02) :235-237

[6] Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization [J].

Gowen, M ;

Lazner, F ;

Dodds, R ;

Kapadia, R ;

Feild, J ;

Tavaria, M ;

Bertoncello, I ;

Drake, F ;

Zavarselk, S ;

Tellis, I ;

Hertzog, P ;

Debouck, C ;

Kola, I .

JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (10) :1654-1663

[7] Recent advances in the synthesis, design and selection of cysteine protease inhibitors [J].

Hernandez, AA ;

Roush, WR .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2002, 6 (04) :459-465

[8] Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis [J].

Hou, WS ;

Brömme, D ;

Zhao, YM ;

Mehler, E ;

Dushey, C ;

Weinstein, H ;

Miranda, CS ;

Fraga, C ;

Greig, F ;

Carey, J ;

Rimoin, DL ;

Desnick, RJ ;

Gelb, BD .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (05) :731-738

[9] MOLECULAR-CLONING OF HUMAN CDNA FOR CATHEPSIN-K - NOVEL CYSTEINE PROTEINASE PREDOMINANTLY EXPRESSED IN BONE [J].

INAOKA, T ;

BILBE, G ;

ISHIBASHI, O ;

TEZUKA, K ;

KUMEGAWA, M ;

KOKUBO, T .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 206 (01) :89-96

[10] IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS [J].

JONES, TA ;

ZOU, JY ;

COWAN, SW ;

KJELDGAARD, M .

ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 :110-119