Decompartmentalizing target validation - Thinking outside the pipeline boxes

Journal of Molecular Medicine

Volumn 84, Issue 10, 2006, Pages 802-813

  Hooft Van Huijsduijnen, Rob ^a   Rommel, Christian ^a  

^a SERONO PHARMACEUTICAL RES INSTITUTE   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANTICOAGULANT AGENT; COMPLEMENTARY DNA; DICOUMAROL; HYDROXAMIC ACID; MIFEPRISTONE; PACLITAXEL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PROTEIN TYROSINE KINASE INHIBITOR; ROSIGLITAZONE; SMALL INTERFERING RNA; TETRAHYDROLIPSTATIN; TROGLITAZONE; VASCULOTROPIN INHIBITOR; WARFARIN;

CENTRAL NERVOUS SYSTEM; DRUG INDUSTRY; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG TARGETING; GENE EXPRESSION; GENETIC TRANSCRIPTION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN GENOME; HYPOTHESIS; LIVER TOXICITY; MEDICAL RESEARCH; MOLECULAR BIOLOGY; MOLECULAR CLONING; NONHUMAN; PHENOTYPE; POSTMARKETING SURVEILLANCE; PROTEIN PROCESSING; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; VALIDATION PROCESS;

ANIMALS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; REPRODUCIBILITY OF RESULTS; TECHNOLOGY, PHARMACEUTICAL;

EID: 33749248536     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00109-006-0080-2     Document Type: Review

References (47)

1. Fishman MC, Porter JA (2005) Pharmaceuticals: a new grammar for drug discovery. Nature 437(7058):491-493
2. Avorn J (2005) Powerful medicines - the benefits, risks and costs of prescription drugs. Vintage/Random House, New York
3. Goozner M (2004) The $800 million pill: the truth behind the cost of new drugs. University of California Press
4. Espanel X, Wälchli S, Pescini Gobert R, El Alama M, Curchod M-L, Gullu-Isler N, Hooft van Huijsduijnen R (2001) Pulling strings below the surface: hormone receptor signaling through inhibition of protein tyrosine phosphatases. Endocrine 15(1):19-28
5. Hooft van Huijsduijnen R, van Loon L, Bol J (1986) cDNA cloning of six mRNAs induced by TMV infection of tobacco and a characterization of their translation products. EMBO J 5:2057-2061
6. Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, Romans KE, Choti MA, Lengauer C, Kinzler KW, Vogelstein B (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294(5545):1343-1346
7. Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300 (5893):611-615
8. Kalinec GM, Fernandez-Zapico ME, Urrutia R, Esteban-Cruciani N, Chen S, Kalinec F (2005) Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss. Proc Natl Acad Sci U S A 102(44):16019-16024
9. Holden C (2004) The origin of speech. Science 303(5662):1316-1319
10. Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD (2005) Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci U S A 102(27):9643-9648
11. Patrucco E, Notte A, Barberis L, Selvetella G, Maffei A, Brancaccio M, Marengo S, Russo G, Azzolino O, Rybalkin SD, Silengo L, Altruda F, Wetzker R, Wymann MP, Lembo G, Hirsch E (2004) PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and-independent effects. Cell 118(3):375-387
12. Gao L, Zhang J (2003) Why are some human disease-associated mutations fixed in mice? Trends Genet 19(12):678-681
13. Zambrowicz BP, Turner CA, Sands AT (2003) Predicting drug efficacy: knockouts model pipeline drugs of the pharmaceutical industry. Curr Opin Pharmacol 3(5):563-570
14. Zambrowicz BP, Sands AT (2003) Knockouts model the 100 bestselling drugs - will they model the next 100? Nat Rev Drug Discov 2(1):38-51
15. Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26(2):99-109
16. Shokat K, Velleca M (2002) Novel chemical genetic approaches to the discovery of signal transduction inhibitors. Drug Discov Today 7(16):872-879
17. Kung C, Shokat KM (2005) Small-molecule kinase-inhibitor target assessment. Chembiochem 6(3):523-526
18. Yu CC, Yen TS, Lowell CA, DeFranco AL (2001) Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn. Curr Biol 11(1):34-38
19. Hibbs ML, Harder KW, Armes J, Kountouri N, Quilici C, Casagranda F, Dunn AR, Tarlinton DM (2002) Sustained activation of Lyn tyrosine kinase in vivo leads to autoimmunity. J Exp Med 196(12):1593-1604
20. Aderem A (2005) Systems biology: its practice and challenges. Cell 121(4):511-513
21. Fasco MJ, Preusch PC, Hildebrandt E, Suttie JW (1983) Formation of hydroxyvitamin K by vitamin K epoxide reductase of warfarin-resistant rats. J Biol Chem 258(7):4372-4380
22. Rioux JD, Abbas AK (2005) Paths to understanding the genetic basis of autoimmune disease. Nature 435(7042):584-589
23. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM, Conn MT, Chang M, Chang SY, Saiki RK, Catanese JJ, Leong DU, Garcia VE, McAllister LB, Jeffery DA, Lee AT, Batliwalla F, Remmers E, Criswell LA, Seldin MF, Kastner DL, Amos CI, Sninsky JJ, Gregersen PK (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75(2):330-337
24. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW (2004) Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 75(3):504-507
25. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36(4):337-338
26. Viken MK, Amundsen SS, Kvien TK, Boberg KM, Gilboe IM, Lilleby V, Sollid LM, Forre OT, Thorsby E, Smerdel A, Lie BA (2005) Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes Immun 6(3):271-273
27. Jagiello P, Aries P, Arning L, Wagenleiter SE, Csernok E, Hellmich B, Gross WL, Epplen JT (2005) The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. Arthritis Rheum 52(12):4039-4043
28. Siminovitch KA (2004) PTPN22 and autoimmune disease. Nat Genet 36(12):1248-1249
29. Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM (1999) Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood 93(6):2013-2024
30. Hasegawa K, Martin F, Huang G, Tumas D, Diehl L, Chan AC (2004) PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells. Science 303(5658):685-689
31. Vang T, Congia M, Macis MD, Musumeci L, Orru V, Zavattari P, Nika K, Tautz L, Tasken K, Cucca F, Mustelin T, Bottini N (2005) Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 37(12):1317-1319
32. Mori M, Yamada R, Kobayashi K, Kawaida R, Yamamoto K (2005) Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. J Hum Genet 50(5):264-266
33. Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, Pape J, Cheshier RC, Murphy PM (2006) CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med 203(1):35-40
34. Lee C (2005) Vive la difference! Nat Genet 37(7):660-661
35. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494-498
36. Grimm D, Kay MA (2006) Therapeutic short hairpin RNA expression in the liver: viral targets and vectors. Gene Ther 13 (6):563-575
37. Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM, Lieberman J (2006) An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439 (7072):89-94
38. Moffat J, Sabatini DM (2006) Building mammalian signalling pathways with RNAi screens. Nat Rev Mol Cell Biol 7(3):177-187
39. Brummelkamp TR, Nijman SM, Dirac AM, Bernards R (2003) Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 424(6950):797-801
40. Li J, Burmeister M (2005) Genetical genomics: combining genetics with gene expression analysis. Hum Mol Genet 14:R163-R169 (Spec No. 2)
41. Jeffrey KL, Brummer T, Rolph MS, Liu SM, Callejas NA, Grumont RJ, Gillieron C, Mackay F, Grey S, Camps M, Rommel C, Gerondakis SD, Mackay CR (2006) Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1. Nat Immunol 7(3):274-283
42. Barber DF, Bartolome A, Hernandez C, Flores JM, Redondo C, Fernandez-Arias C, Camps M, Ruckle T, Schwarz MK, Rodriguez S, Martinez AC, Balomenos D, Rommel C, Carrera AC (2005) PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat Med 11(9):933-935
43. Camps M, Ruckle T, Ji H, Ardissone V, Rintelen F, Shaw J, Ferrandi C, Chabert C, Gillieron C, Francon B, Martin T, Gretener D, Perrin D, Leroy D, Vitte PA, Hirsch E, Wymann MP, Cirillo R, Schwarz MK, Rommel C (2005) Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 11(9):936-943
44. Terszowski G, Muller SM, Bleul CC, Blum C, Schirmbeck R, Reimann J, Pasquier LD, Amagai T, Boehm T, Rodewald HR (2006) Evidence for a functional second thymus in mice. Science 312(5771):284-287
45. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860-867
46. Becker J (2004) Signal transduction inhibitors - a work in progress. Nat Biotechnol 22(1):15-18
47. Frantz S (2005) Drug discovery: playing dirty. Nature 437 (7061):942-943