Development of small-molecule therapies for autoimmune diseases

Autoimmunity

Volumn 43, Issue 7, 2010, Pages 526-538

  Bürli, Roland W ^a   Haughan, Alan F ^a   Hodges, Alastair J ^a  

^a BioFocus DPI   (United Kingdom)

Author keywords

Hit discovery; hit to lead; lead optimization

Indexed keywords

CYTOCHROME P450; FINGOLIMOD; G PROTEIN COUPLED RECEPTOR; NATALIZUMAB; THERMOZYMOCIDIN;

AUTOIMMUNE DISEASE; CHEMICAL STRUCTURE; DRUG EFFICACY; DRUG SAFETY; DRUG STRUCTURE; FOLLOW UP; GENOTOXICITY; IMMUNOCOMPETENT CELL; LIVER MICROSOME; MOLECULAR THERAPY; MOLECULARLY TARGETED THERAPY; MULTIPLE SCLEROSIS; PROTEIN TARGETING; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; AUTOIMMUNE DISEASES; DRUG DESIGN; HUMANS; IMMUNOSUPPRESSIVE AGENTS;

EID: 77958015593     PISSN: 08916934     EISSN: 1607842X     Source Type: Journal    
DOI: 10.3109/08916931003674758     Document Type: Review

References (68)

1. Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009;373:659-672.
2. Cornillie F. Ten years of infliximab (Remicade) in clinical practice: The story from bench to bedside. Eur J Pharmacol 2009;623(Suppl. 1):S1-S4.
3. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacol Ther 2008;117:244-279.
4. Stoll JG, Yasothan U. Rheumatoid arthritis market. Nat Rev Drug Discov 2009;8:693-694.
5. Reich K, Yasothan U, Kirkpatrick P. Ustekinumab. Nat Rev Drug Discov 2009;8:355-356.
6. Scheinecker C, Smolen J, Yasothan U, Stoll J, Kirkpatrick P. Tocilizumab. Nat Rev Drug Discov 2009;8:273-274.
7. Guercan H, Keskin DB, Stern JNH, Nitzberg MA, Shekhani H, Ahmed AR. A review of the current use of Rituximab in autoimmune diseases. Int Immunopharmacol 2009;9:10-25.
8. Kieseier BC, Wiendl H, Leussink VI, Stüve O. Immunomo-dulatory treatment strategies in multiple sclerosis. J Neurol 2008;255:15-21.
9. Mertens M, Singh JA. Anakinra for rheumatoid arthritis: A systematic review. J Rheumatol 2009;36:1118-1125.
10. Keller TH, Pichota A, Yin Z. A practical view of 'drugability'. Curr Opin Chem Biol 2006;10:357-361.
11. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002;1:727-730.
12. Bleicher KH, Nettekoven M, Peters JU, Wyler R. Lead generation: Sowing the seeds for future success. Chimia 2004; 58:588-600.
13. Lafreniere RG, MacDonald MLE, Dube M-P, MacFarlane J, O'Driscoll M, Brais B, Meilleur S, Brinkman RR, Dadivas O, Pape T, Platon C, Radomski C, Risler J, Thompson J, Guerra-Escobio A-M, Davar G, Breakefield XO, Pimstone SN, Green R, Pryse-Phillips W, Goldberg YP, Younghusband HB, Hayden MR, SherringtonR, Rouleau GA, Samuels ME. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates. Am J Hum Genet 2004; 74:1064-1073.
14. Halapi E, Hakonarson H. Population genomics of drug response. Am. J. Pharmacogenomics 2004;4:73-82.
15. Duarte CD, Barreiro EJ, Fraga CAM. Privileged structures: A useful concept for the rational design of new lead drug candidates. Mini-Rev Med Chem 2007;7:1108-1119.
16. Harris CJ. Letting the target determine your compound acquisition strategy. Drug Discov World 2009:19-22.
17. Harris CJ, Stevens AP. Chemogenomics: Structuring the drug discovery process to gene families. Drug Discov Today 2006; 11:880-888.
18. Birault V, Harris CJ, Le J, Lipkin M, Nerella R, Stevens A. Bringing kinases into focus: Efficient drug design through the use of chemogenomic toolkits. Curr Med Chem 2006;13: 1735-1748.
19. Lipkin MJ, Stevens AP, Livingstone DJ, Harris CJ. How large does a compound screening collection need to be? Comb Chem High Throughput Screen 2008;11:482-493.
20. Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Drug Discov 2005;4:206-220.
21. Abel U, Koch C, Speitling M, Hansske FG. Modern methods to produce natural-product libraries. Curr Opin Chem Biol 2002;6:453-458.
22. Borel JF. History of the discovery of cyclosporin and of its early pharmacological development. Wien Klin Wochenschr 2002; 114:433-437.
23. Congreve M, Chessari G, Tisi D, Woodhead AJ. Recent developments in fragment-based drug discovery. J Med Chem 2008;51:3661-3680.
24. Lajiness MS, Maggiora GM, Shanmugasundaram V. Assessment of the consistency of medicinal chemists in reviewing sets of compounds. J Med Chem 2004;47:4891-4896.
25. Rishton GM. Non-leadlikeness and leadlikeness in biochemical screening. Drug Discov Today 2002;8:86-96.
26. Hopkins AL, Groom CR, Alex A. Ligand efficiency: A useful metric for lead selection. Drug Discov Today 2004;9: 430-431.
27. Bembenek SD, Tounge BA, Reynolds CH. Ligand efficiency and fragment-based drug discovery. Drug Discov Today 2009; 14:278-283.
28. Rees DC, Congreve M, Murray CW, Carr R. Fragment-based lead discovery. Nat Rev Drug Discov 2004;3:660-672.
29. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3-25.
30. Cruciani G, Carosati E, De Boeck B, Ethirajulu K, Mackie C, Howe T, Vianello R. MetaSite: Understanding metabolism in human cytochromes from the perspective of the chemist. J Med Chem 2005;48:6970-6979.
31. Blake JF. Chemoinformatics-Predicting the physicochemical properties of 'drug-like' molecules. Curr Opin Biotechnol 2000;11:104-107.
32. Livingstone DJ, Van De Waterbeemd H. In silico prediction of human bioavailability. Meth Prin Med Chem 2009;40: 433-451.
33. Van de Waterbeemd H. Physicochemical properties in drug profiling. Meth Prin Med Chem 2008;37:25-52.
34. Tyrchan C, Blomberg N, Engkvist O, Kogej T, Muresan S. Physicochemical property profiles of marketed drugs, clinical candidates and bioactive compounds. Bioorg Med Chem Lett 2009;19:6943-6947.
35. Wunberg T, Hendrix M, Hillisch A, Lobell M, Meier H, Schmeck C, Wild H, Hinzen B. Improving the hit-to-lead process: Data-driven assessment of drug-like and lead-like screening hits. Drug Discov Today 2006;11:175-180.
36. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA, Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL, Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C, Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS, Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ, Johnson KS, Nelms LF, Des Etages SG, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL, Larson M, Si MS, Paniagua R, Higgins J, Holm B, Reitz B, Zhou YJ, Morris RE, O'Shea JJ, Borie DC. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003;302:875-878.
37. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008;26:127-132.
38. Milici AJ, Kudlacz EM, Audoly L, Zwillich S, Changelian P. Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Res Ther 2008;10:R14.
39. Boy MG, Wang C, Wilkinson BE, Chow VF-S, Clucas AT, Krueger JG, Gaweco AS, Zwillich SH, Changelian PS, Chan G. Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol 2009;129: 2299-2302.
40. Quaedackers ME, Mol W, Korevaar SS, van Gurp EAFJ, van IJcken WFJ, Chan G, Weimar W, Baan CC. Monitoring of the immunomodulatory effect of CP-690,550 by analysis of the JAK/STAT pathway in kidney transplant patients. Transplantation 2009;88:1002-1009.
41. Lin Q, Meloni D, Pan Y, Xia M, Rodgers J, Shepard S, Li M, Galya L, Metcalf B, Yue T-Y, Liu P, Zhou J. Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction. Org Lett 2009;11: 1999-2002.
42. Stoll JG, Yasothan U. Rheumatoid arthritis market. Nat Rev Drug Discov 2009;8:693-694.
43. Pine PR, Chang B, Schoettler N, Banquerigo ML, Wang S, Lau A, Zhao F, Grossbard EB, Payan DG, Brahn E. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol 2007;124:244-257.
44. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. R406, an orally available spleen tyrosine kinase inhibitor blocks Fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 2006;319:998-1008.
45. Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, Bussel JB. Of mice and men: An open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 2009;113:3154-3160.
46. Weinblatt ME, KavanaughA,Burgos-VargasR,DikranianAH, Medrano-Ramirez G, Morales-Torres JL, Murphy FT, Musser TK, Straniero N, Vicente-Gonzales AV, Grossbard E. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: A twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 2008;58:3309-3318.
47. Bahjat FR, Pine PR, Reitsma A, Cassafer G, Baluom M, Grillo S' Chang B, Zhao FF, Payan DG, Grossbard EB, Daikh DI. An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus. Arthritis Rheum 2008;58:1433-1444.
48. Dambach DM. Potential adverse effects associated with inhibition of p38 a/b MAP kinases. Curr Top Med Chem 2005;5(10):929-939.
49. Goldstein DM, Gabriel T. Pathway to the clinic: Inhibition of P38 MAP kinase. A review of ten chemotypes selected for development. Curr Top Med Chem 2005;5(10):1017-1029.
50. Yong HY, Koh MS, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Invest Drugs 2009;12:1893-1905.
51. Steinman L. Blocking adhesion molecules as therapy for multiple sclerosis: Natalizumab. Nat Rev Drug Discov 2005;4: 510-518.
52. Honey K. The comeback kid: TYSABRI now FDA approved for Crohn disease. J Clin Invest 2008;118(3):825-826.
53. Davenport RJ, Munday JR. Alpha4-integrin antagonism-An effective approach for the treatment of inflammatory diseases? Drug Discov Today 2007;12(13/14):569-576.
54. Trial watch: Phase III promise for oral multiple sclerosis therapy Nat Rev Drug Discov 2009;8:98-99.
55. Fujita T, Inoue K, Yamamoto S, Ikumoto T, Sasaki S, Toyama R, Chiba K, Hoshino Y, Okumoto T. Fungal metabolites. Part II. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot 1994;47: 208-215.
56. Kluepfel D, Bagli J, Baker H, Charest MP, Kudelski A. Myriocin, a new antifungal antibiotic from Myriococcum albomyces. J Antibiot 1972;25:109-115.
57. Bagii JF, Kluepfel D, St. Jacques M. Elucidation of structure and stereochemistry of myriocin. Novel antifungal antibiotic. J Org Chem 1973;38:1253-1260.
58. Aragozzini F, Manachini PL, Craveri R, Rindone B, Scolastico C. Isolation and structure determination of a new antifungal a-(hydroxymethyl)-a-amino acid. Tetrahedron 1972;28:5493-5498.
59. Fujita T, Yoneta M, Hirose R, Sasaki S, Inoue K, Kiuchi M, Hirase S, Adachi K, Arita M, Chiba K. Simple compounds, 2-alkyl-2-amino-1,3-propanediols have potent immunosup-pressive activity. Bioorg Med Chem Lett 1995;5:847-852.
60. Adachi K, Kohara T, Nakao N, Arita M, Chiba K, Mishina T, Sasaki S, Fujita T. Design, synthesis, and structure-activity relationships of 2-substituted-2-amino-1,3-propanediols: Discovery of a novel immunosuppressant, FTY720. Bioorg Med Chem Lett 1995;5:853-856.
61. Adachi K, Chiba K. FTY720 story. Its discovery and the following accelerated development of sphingosine-1-phosphate receptor agonists as immunomodulators based on reverse pharmacology. Perspect Medicin Chem 2007;1:11-23.
62. Miyake Y, Kozutsumi Y, Nakamura S, Fujita T, Kawasaki T. Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-I/myriocin. Bio-chem Biophys Res Commun 1995;211:396-403.
63. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, Hale J, Lynch CL, Rupprecht K, Parsons W, Rosen H. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002;296:346-349.
64. Forrest M,Sun SY, Hajdu R, BergstromJ,CardD, Doherty G, Hale J, Keohane C, Meyers C, Milligan J, Mills S, Nomura N, Rosen H, Rosenbach M, Shei G-J, Singer II, Tian M, West S, White V, Xie J, Proia RL, Mandala S. Immune cell regulation and cardiovascular effects of sphingosine-1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther 2004;309:758-768.
65. Hale JJ, Lynch CL, Neway W, Mills SG, Hajdu RK, Carol A, Rosenbach MJ, Milligan JA, Shei GJ, Parent SA, Chrebet G, Bergstrom J, Card D, Ferrer M, Hodder P, Strulovici B, Rosen H, Mandala S. A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate receptor agonists. J Med Chem 2004;47:6662-6665.
66. Evindar G, Satz AL, Bernier SG, Kavarana MJ, Doyle E, Lorusso J, Taghizadeh N, Halley K, Hutchings A, Kelley MS, Wright AD, Saha AK, Hannig G, Morgan BA, Westlin WF. Synthesis and evaluation of arylalkoxy-and biarylalkoxy-phenylamide and phenylimidazoles as potent and selective sphingosine-1-phosphate receptor subtype-1 agonists. Bioorg Med Chem Lett 2009;19:2315-2319.
67. Zhu R, Snyder AH, Kharel Y, Schaffter L, Sun Q, Kennedy PC, Lynch KR, Macdonald TL. Asymmetric synthesis of conformationally constrained Fingolimod analogues-Discovery of an orally active sphingosine-1-phosphate receptor type-1 agonist and receptor type-3 antagonist. J Med Chem 2007;50:6428-6435.
68. Zécri FJ, Albert R, Landruma G, Hinterding K, Cooke NG, Guerini D, Streiff M, Bruns C, Nuesslein-Hildesheim B. Pyrazole derived from (\+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P1) receptor agonists. Bioorg Med Chem Lett 2010;20:35-37.