Emerging techniques for the discovery and validation of therapeutic targets for skeletal diseases

Expert Opinion on Therapeutic Targets

Volumn 6, Issue 6, 2002, Pages 679-689

  CHo, Christine H ^a   Nuttall, Mark E ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Cartilage; Osteoarthritis; Osteoblasts; Osteoporosis

Indexed keywords

ANABOLIC AGENT; AP 22408; CASPASE; CASPASE INHIBITOR; CATHEPSIN B; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; CGP 77675; COLLAGEN TYPE 1; COMPLEMENTARY DNA; CPG 77675; CYSTEINE PROTEINASE INHIBITOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; HORMONE; INTERLEUKIN 6; MESSENGER RNA; NVP AAK 980; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PARATHYROID HORMONE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT PROTEIN; SB 357114; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TRANSCRIPTION FACTOR EGR 1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMIN D;

ARTHROPATHY; BIOINFORMATICS; BONE DISEASE; CELL ASSAY; CELL POPULATION; CHRONIC DISEASE; COMBINATORIAL CHEMISTRY; DNA LIBRARY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG SAFETY; DRUG STRUCTURE; FEMALE; GENE EXPRESSION; GENE IDENTIFICATION; GENE OVEREXPRESSION; GENETIC ANALYSIS; GENOMICS; HORMONE SUBSTITUTION; HUMAN; HYPERCALCEMIA; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; MEDICAL TECHNOLOGY; MOUSE; NONHUMAN; OSTEOARTHRITIS; OSTEOPOROSIS; PROTEIN FUNCTION; PROTEOMICS; REVIEW; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; TISSUE SECTION; TRANSGENICS; VALIDATION PROCESS;

ANIMALS; BONE DISEASES; CARRIER PROTEINS; CASPASES; CATHEPSINS; CYSTEINE PROTEINASE INHIBITORS; DNA-BINDING PROTEINS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; EARLY GROWTH RESPONSE PROTEIN 1; GENOMICS; GLYCOPROTEINS; HUMANS; IMMEDIATE-EARLY PROTEINS; MEMBRANE GLYCOPROTEINS; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; MOLECULAR STRUCTURE; OSTEOARTHRITIS; OSTEOPOROSIS; OSTEOPROTEGERIN; PROTEOMICS; RANK LIGAND; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, TUMOR NECROSIS FACTOR; SRC-FAMILY KINASES; TRANSCRIPTION FACTORS; TWO-HYBRID SYSTEM TECHNIQUES;

EID: 0036927138     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.6.6.679     Document Type: Review

References (50)

1. JOHNSTON PA, JOHNSTON PA: Cellular platforms for HTS: three case studies. Drug Disc. Today (2002) 7:353-363.
2. VEBER DF, DRAKE FH, GOWEN M: The new partnership of genomics and chemistry for accelerated drug development. Curr. Opin. Chem. Biol (1997) 1:151-156
3. GORDON EM, BARRETT RW, DOWER WJ, FODOR SPA, GALLOP MA. Applications of combinatorial technologies to drug discovery: combinatorial organic synthesis, library screening strategies and future directions. J. Med. Chem. (1994) 37:1385-1401.
4. ALI M, MARKHAM AF, ISAACS JD: Application of differential display to immunological research. J. Immunol. Methods (2001) 250:29-43.
5. WANG FL, CONNOR JR, DODDS RA et al: Differential expression of egr-1 in osteoarthritic compared to normal adult human articular cartilage. 0steoarthritis Cartilage (2000) 8:161-169.
6. INAOKA T, BILBE G, ISHIBASHI O et al.: Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone. Biochem. Biophys. Res. Commun. (1995) 206:89-96.
7. BROMME D, OKAMOTO K, WANG BB et al.: Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda and characterization of the enzyme. J. Biol, Chem. (1996) 271:2126-2632.
8. DRAKE FH, DODDS RA, JAMES IE et al.: Cathepsin K, but not cathepsin B, L, or S, is abundantly expressed in human osteoclasts. J. Biol. Chem. (1996) 271:12511-12516.
9. GARNER P, BOREL O, BYRJALSEN I et al.: The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J. Biol. Chem. (1998) 273:32347-32352.
10. LJUSBERG J, DODDS RA, LARK MW et al.: Tartarate-resistant acid phosphatase is proteolytically cleaved in vivo by cathepsin K. J. Bone Miner. Res. (1999) 14(Suppl. 1):S358.
11. BOSSARD MJ, TOMASZEK TA, THOMPSON SK et at: Proteolytic activity of human osteoclast cathepsin K. J. Biol. Chem. (1996) 271:12517-12524.
12. XIA L, KILB J, WEX H et al.: Localization of rat cathepsin K in osteoclasts and resorption pits: inhibition of bone resorption and cathepsin K-activity by peptidyl vinyl sulfones. Biol. Chem. (1999) 380:679-687.
13. INUI T, ISHIBASHI O, INAOKA T et al.: Cathepsin K antisense oligodoexynucleotide inhibits osteoclastic bone resorption. J. Biol. Chem. (1997) 272:8109-8112.
14. GOWEN M, LAZNER F, DODDS R et al.: Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J. Bone Miner. Res. (1999) 14:1654-1663.
15. THOMPSON SK, HALBERT SM, BOSSARD MJ et al.: Design of potent and selective human cathepsin K inhibitors that span the active site. Proc. Not Acad. Sci. USA (1997) 94:14249-14254.
16. STROUP GB, LARK MW, VEBER DF et al.: Potent and selective inhibition of human cathepsin K leads to inhibition of bone resorption in vivo in a nonhuman primate. J Bone Miner. Res. (2001) 16:1739-1746.
17. TSUDA E, GOTO M, MOCHIZUKI S et al.: Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem. Biophys. Res. Commun. (1997) 234:137-142.
18. SIMONET WS, LACEY DL, DUNSTAN CR et al.: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell (1997) 89:309-319.
19. COCKETT M, DRACOPOLI N, SIGAL E: Applied genomics: integration of the technology within pharmaceutical research and development. Curr Opin. Biotech. (2000) 11:602-609.
20. BUCAY N, SAROSI I, DUNSTAN CR et al.: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. (1998) 12:1260-1268.
21. MIZUNO A, AMIZUKA N, IRIE K et al.: Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res. Commun. (1998) 247:610-615.
22. LACEY DL, TIMMS E, TAN HL et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell (1998) 93:165-176.
23. YASUDA H, SHIMA N, NAKAGAWA N et al.: Osteoclast differentiation factor is a ligand for osteoprotegerin osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL). Proc. Natl. Acad. Sci. USA (1998) 95:3597-3602.
24. WONG BR, RHO J, ARRON J et al.: TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-jun N-terminal kinase in T cells. J. Biol. Chem. (1997) 272:25190-25194.
25. ANDERSON MA, MARASKOVSKY E, BILLINGSLEY WL et al.: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. (1997) 390:175-179.
26. HSU HL, LACEY DL, DUNSTAN CR et al.: Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc. Natt Acad. Sci. USA (1999) 96:3540-3545.
27. MORONEY S, CAPPARELLI C, LEE R et al.: A chimeric form of the osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-beta, TNF-alpha, PTH, PTHrP and 1,25(OH)(2)D-3. J. Bone Miner. Res. (1999) 14:1478-1485.
28. BEKKER PJ, HOLLOWAY D, NAKANISHI A et al.: Osteoprotegerin (OPG) has potent and sustained anti-resorptive activity in postmenopausal women. J. Bone Miner. Res. (1999) 14(Suppl. 1):S180.
29. ELLIS HM, HORVITZ HR: Genetic control of programmed cell death in the nematode C. elegans. Cell (1986) 44:817-829.
30. LEE D, LONG SA, ADAMS JL et al.: Potent and selective nonpeptide inhibitors of caspase 3 and 7 inhibit apoptosis and maintain cell functionality. J. Biol. Chem. (2000) 270:16007-16014.
31. KOURI JB, ROSALES-ENCINA JL, CHAUDHURI PP, LUNA J, MENA R: Apoptosis in human osteoarthritic cartilage: a microscopy report. Med Sci. Res. (1997) 25:245-248.
32. BLANCO FJ, OCHS RL, SCHWARTZ H, LOTZ M: Chondrocyte apoptosis induced by nitric oxide. Am. J. Pathol. (1995) 146:75-85.
33. HASHIMOTO S, OCHS RL, KOMIYA S, LOTZ M: Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. (1998) 41:1632-1638.
34. MANKIN H, DORFMAN H, LIPPIELLO L, ZARINS A. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips: correlation of morphology and metabolic data. J. Bone Joint. Surg. (1971) 53:523-537.
35. VIOLETTE SM, GUAN W, BARTLETT C et al.: Bone-targeted Src SH2 inhibitors block Src cellular activity and osteoclast-mediated resorption. Bone (2001) 28:54-64.
36. MISSBACH M, JESCHKE M, FEYEN J et al.: A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone (1999) 24:437-449.
37. GAMSE R, WIDLER L, MISSBACH M et al.: NVP-AAK980, a novel phenylamino-2-alkylamino-purine derivative, potently inhibits the tyrosine kinase Src and bone resorption. J. Bone Miner. Res. (1999) 14(Suppl. 1):S497.
38. SORIANO P, MONTGOMERY C, GESKE R et al.: Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell (1991) 64:693-702.
39. BOYCE BF, YONEDA T, LOWE C et al.: Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J. Clin. Invest. (1992) 90:1622-1627.
40. NYMAN TA: The role of mass spectrometry in proteome studies. Biomol. Eng. (2001) 18:221-227.
41. ISSAQ HJ, VEENSTRA TD, CONRADS TP, FELSCHOW D: The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. Biochem. Biophys. Res. Commun. (2002) 292:587-592.
42. AUGEN J: The evolving role of information technology in the drug discovery process. Drug Disc. Today (2002) 7:315-323.
43. YEE A, CHANG X, PINEDA-LUCENA A et al.: An NMR approach to structural proteomics. Proc. Nat. Acad Sci. USA (2002) 99:1825-1830.
44. SOELLICK TR, UHRIG JF: Development of an optimized interaction-mating protocol for large scale yeast two-hybrid analyses. Genome Biol. (2001) 2:0052.1-0052.7.
45. ROSE M, BOTSTEIN D: Construction and use of gene fusions to LacZ (beta-galactosidase) that are expressed in yeast. Methods Enzymol. (1983) 101:167-180.
46. CHIEN CT, BARTEL PL, STERNGLANZ R, FIELDS S: The two-hybrid system: a method to identify and clone genes for proteins that interact with proteins of interest. Proc. Natl. Acad. Sci. USA (1991) 88:9578-9582.
47. MCDONNELL DP CLEMM DL, HERMAN T et al.: Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol. Endocrinol. (1995) 9:659-699.
48. MOSSELMANN S, POLMAN J, DIJKEMA R: ERβ identification and characterization of a novel human estrogen receptor. FEBS Lett. (1996) 392:49-53.
49. THE WRITING GROUP FOR THE PEPI TRIAL: Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin intervention (PEPI) trial. J. Am. Med. Assoc. (1996) 276:1389-1396.
50. NORRIS JD, FAN D, WAGNER BL et al.: Identification of the sequences within the human complement 3 promoter required for estrogen responsiveness provides insight into the mechanism of tamoxifine mixed agonist activity. Mol. Endocrinol. (1996 10:1605-1616.