Use of kv1.3 blockers for inflammatory skin conditions

Current Medicinal Chemistry

Volumn 17, Issue 26, 2010, Pages 2882-2896

  Nguyen, W ^a   Howard, B L ^a   Neale, D S ^a   Thompson, P E ^a   White, P J ^a   Wulff, H ^b   Manallack, D T ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Autoimmune disorder; Drug design; Inflammation; Kv1.3 channel; Psoriasis

Indexed keywords

1 BENZYL 1,4 DIHYDRO 4 PENTYLIMINOQUINOLINE; 4 AMINOPYRIDINE; ALEFACEPT; ANTIPSORIASIS AGENT; CD2 ANTIGEN; CD45RO ANTIGEN; CP 190 325; CP 393223; CP 393224; CP 394322; DILTIAZEM; EFALIZUMAB; ETANERCEPT; INFLIXIMAB; INTERLEUKIN 2 RECEPTOR; NIFEDIPINE; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL KV1.3; PSORALEN; TETRAPHENYLPORPHYRIN DERIVATIVE; TETRYLAMMONIUM; THIENOPYRIDINE DERIVATIVE; UK 78 282; UNCLASSIFIED DRUG; VERAPAMIL; WIN 17317;

ARTICLE; AUTOIMMUNE DISEASE; CD25+ T LYMPHOCYTE; CELL PROLIFERATION; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; HUMAN; IC 50; IMMUNE RESPONSE; MEMORY T LYMPHOCYTE; PATHOGENESIS; PSORIASIS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

DRUG DELIVERY SYSTEMS; HUMANS; KV1.3 POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKERS; PSORIASIS;

EID: 77955617273     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710792065072     Document Type: Article

References (109)

1. Stuve, O.; Marra, C.; Jerome, K.; Cook, L.; Cravens, P.; Cepok, S. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann. Neurol., 2006, 59, 743-747.
2. Van Assche, G.; Van Ranst, M.; Sciot, R.; Dubois, B.; Vermeire, S.; Noman, M. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N. Engl. J. Med., 2005, 353, 362-368.
3. http://www.prweb.com/releases/2009/06/prweb2528754.htm Accessed, August 2009.
4. Fitzpatrick, T.; Johnson, R.; Wolff, K. Color atlas and synopsis of clinical dermatology; 4th ed.; McGraw-Hill: New York, 2001.
5. Marks, R.; Plunkett, A.; Merlin, K.; Jenner, N. Atlas of common skin diseases in Australia; Department of Dermatology, St Vincents Hospital, Melbourne., 1999.
6. Nestle, F.O.; Kaplan, D.H.; Barker, J. Psoriasis. N. Engl. J. Med., 2009, 367, 496-509.
7. Menter, A.; Gottlieb, A.; Feldman, S.R.; Van Voorhees, A.S.; Leonardi, C.L.; Gordon, K.B.; Lebwohl, M.; Koo, J.Y.; Elmets, C.A.; Korman, N.J.; Beutner, K.R.; Bhushan, R. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J. Am. Acad. Dermatol., 2008, 58, 826-850.
8. Gelfand, J.M.; Feldman, S.R.; Stern, R.S.; Thomas, J.; Rolstad, T.; Margolis, D.J. Determinants of quality of life in patients with psoriasis: a study from the US population. J. Am. Acad. Dermatol., 2004, 57, 704-708.
9. Horn, E.J.; Fox, K.M.; Patel, V.; Chiou, C.F.; Dann, F.; Lebwohl, M. Association of patient-reported psoriasis severity with income and employment. J. Am. Acad. Dermatol., 2007, 57, 963-971.
10. Pariser, D.M.; Bagel, J.; Gelfand, J.M.; Korman, N.J.; Ritchlin, C.T.; Strober, B.E.; Van Voorhees, A.S.; Young, M.; Rittenberg, S.; Lebwohl, M.G.; Horn, E.J. National Psoriasis Foundation clinical consensus on disease severity. Arch. Dermatol., 2007, 143, 239-242.
11. Lebwohl, M.; Freeman, A.; Chapman, M.; Feldman, S.; Hartle, J.; Henning, A. Tacrolimus ointment is effective for facial and intertriginous psoriasis. J. Am. Acad. Dermatol., 2004, 57, 723-730.
12. Zanolli, M. Phototherapy arsenal in the treatment of psoriasis. Dermatol. Clin., 2004, 22, 397-406.
13. Luba, K.M.; Stulberg, D.L. Chronic plaque psoriasis. Am. Fam. Phys., 2006, 73, 636-644.
14. Weinstein, G.D.; Jeffes, E.; McCullough, J.L. Cytotoxic and immunologic effects of methotrexate in psoriasis. J. Invest. Dermatol., 1990, 95, 49S-52S.
15. Lee, M.; Kalb, R.E. Systemic therapy for psoriasis. Dermatol. Nurs., 2008, 2, 105-111.
16. Sinclair, R. A new approach to managing moderate to severe chronic plaque psoriasis. Aust. J. Pharm., 2006, 87, 66-69.
17. Kircik, L.H.; Del Rosso, J.Q. Anti-TNF agents for the treatment of psoriasis. J. Drugs Dermatol., 2009, 8, 546-559.
18. Wulff, H.; Pennington, M. Targeting effector memory T-cells with Kvl.3 blockers. Curr. Opin. DrugDiscov. Dev., 2007, 10, 438-445.
19. Wulff, H.; Zhorov, B.S. K+ channel modulators for the treatment of neurological disorders and autoimmune diseases. Chem. Rev., 2008, 108, 1744-1773.
20. Vena, G.A.; Cassano, N. Emerging drugs for psoriasis. Expert Opin. Emerg. Drugs, 2006, 11, 567-596.
21. Prinz, J.C. The role of T cells in psoriasis. J. Eur. Acad. Derm. Vener., 2003, 17, 257-270.
22. Sagoo, G.S.; Tazi-Ahnini, R.; Barker, J.W.; Elder, J.T.; Nair, R.P.; Samuelsson, L.; Traupe, H.; Trembath, R.C.; Robinson, D.A.; Iles, M.M. Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosomes 6p21 and 4q28-q31 in Caucasian and Chinese Hans population. J. Invest. Dermatol., 122, 1401-1405.
23. Bowcock, A.M.; Krueger, J.G. Getting under the skin: the immunogenetics of psoriasis. Nat. Rev. Immunol., 2005, 5, 699-711.
24. Gottlieb, A.B.; Lebwohl, M.; Shirin, S.; Sherr, A.; Gilleaudeau, P.; Singer, G.; Solodkina, G.; Grossman, R.; Gisoldi, E.; Phillips, S.; Neisler, H.M.; Krueger, J.G. Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study. J. Am. Acad. Dermatol., 2000, 43, 595-604.
25. Wrone-Smith, T.; Nickoloff, B.J. Dermal injection of immunocytes induces psoriasis. J. Clin. Invest., 1996, 98, 1878-1887.
26. Prinz, J.C.; Groß, B.; Vollmer, B.S.; Trommler, P.; Strobel, I.; Meurer, M.; Plewig, G. T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products. Eur. J. Immunol., 1994, 24, 593-598.
27. Sallusto, F.; Lenig, D.; Förster, R.L., M.; Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature, 1999, 401, 708-712.
28. Geginat, J.; Sallusto, F.; Lanzavecchia, A. Cytokine-driven proliferation and differentiation of human naïve, central memory and effector memory CD4+ T cells. Pathol. Biol., 2003, 51, 64-66.
29. Baccala, R.; Theofilopoulos, A.N. The new paradigm of T-cell homeostatic proliferation-induced autoimmunity. Trends Immunol., 26, 5-8.
30. Chandy, G.K., Wulff, H., Beeton, C., Calabresi, P. A., Gutman, G. A., Pennington., M. In Voltage-Gated Ion Channels as Drug Targets; Triggle, D., Ed.; Wiley-VCH Verlag GmbH & Co.: New York, 2006; pp. 214-274.
31. Wulff, H.; Calabresi, P.A.; Allie, R.; Yun, S.; Pennington, M.; Chandy, G.K. The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. J. Clin. Invest., 2003, 111, 1703-1713.
32. Wulff, H.; Beeton, C.; Chandy, K.G. Potassium channels as therapeutic targets for autoimmune disorders. Curr. Opin. Drug Discov. Dev., 2003, 6, 640-647.
33. Chandy, K.G.; Cahalan, M.; Pennington, M.; Norton, R.S.; Wulff, H.; Gutman, G.A. Potassium channels in T lymphocytes: toxins to therapeutic immunosuppressants. Toxicon, 2001, 39, 1269-1276.
34. Chandy, K.G.; Wulff, H.; Beeton, C.; Pennington, M.; Gutman, G.A.; Cahalan, M.D. K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci., 2004, 25, 280-289.
35. 2+ store to the plasma membrane. Nature, 2005, 437, 902-905.
36. Prakriya, M.; Feske, S.; Gwack, Y.; Srikanth, S.; Rao, A.; Hogan, P.G. Orai1 is an essential pore subunit of the CRAC channel. Nature, 2006, 443, 230-233.
37. Cahalan, M.D.; Chandy, K.G. The functional network of ion channels in T lymphocytes. Immunol. Rev., 2009, 231, 59-87.
38. Cahalan, M.D.; Wulff, H.; Chandy, K.G. Molecular properties and physiological roles of ion channels in the immune system. J. Clin. Immunol., 2001, 21, 235-252.
39. Lin, C.S.; Boltz, R.C.; Blake, J.T.; Nguyen, M.; Talento, A.; Fischer, P.A.; Springer, M.S.; Sigal, N.H.; Slaughter, R.S.; Garcia, M.L. Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation. J. Exp. Med., 1993, 177, 637-645.
40. DeCoursey, T.E.; Chandy, K.G.; Gupta, S.; Cahalan, M.D. Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis? Nature, 1984, 307, 465-468.
41. Wulff, H.; Knaus, H.G.; Pennington, M.; Chandy, K.G. K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity. J. Immunol., 2004, 173, 776-786.
42. Rangaraju, S.; Chi, V.; Pennington, M.W.; Chandy, K.G. Kv1.3 potassium channels as a therapeutic target in multiple sclerosis. Expert Opin. Ther. Targets, 2009, 13, 909-924.
43. Krueger, J.G. The immunologic basis for the treatment of psoriasis with new biologic agents. J. Am. Acad. Dermatol., 2002, 46, 1-23.
44. Vissers, W.H.; Arndtz, C.H.; Muys, L.; Van Erp, P.E.; de Jong, E.M.; van de Kerkhof, P.C. Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late. Br. J. Dermatol., 2004, 150, 852-859.
45. Ghoreschi, K.; Thomas, P.; Breit, S.; Dugas, M.; Mailhammer, R.; van Eden, W.; van der Zee, R.; Biedermann, T.; Prinz, J.; Mack, M.; Mrowietz, U.; Christophers, E.; Schlondorff, D.; Plewig, G.; Sander, C.A.; Rocken, M. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat. Med., 2003, 9, 40-46.
46. Austin, L.M.; Ozawa, M.; Kikuchi, T.; Walters, I.B.; Krueger, J.G. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J. Invest. Dermatol., 1999, 113, 752-759.
47. Chamian, F.; Lin, S.L.; Lee, E.; Kikuchi, T.; Gilleaudeau, P.; Sullivan-Whalen, M.; Cardinale, I.; Khatcherian, A.; Novitskaya, I.; Wittkowski, K.M.; Krueger, J.G.; Lowes, M.A. Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J. Transl. Med., 2007, 5, 27.
48. Sobell, J.M.; Kalb, R.E.; Weinberg, J.M. Management of moderate to severe plaque psoriasis (part 2): clinical update on T-cell modulators and investigational agents. J. Drugs Dermatol., 2009, 8, 230-238.
49. Sobell, J.M.; Kalb, R.E.; Weinberg, J.M. Management of moderate to severe plaque psoriasis (part I): clinical update on antitumor necrosis factor agents. J. Drugs Dermatol., 2009, 8, 147-154.
50. Breland, A.E.; Currier, R.D. Scorpion venom and multiple sclerosis. Lancet, 1983, 2, 1021.
51. Miller, C.; Moczydlowski, E.; Latorre, R.; Phillips, M. Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature, 1985, 313, 316-318.
52. Sands, S.; Lewis, R.; Cahalan, M. Charybdotoxin blocks voltage-gated K+ channels in human and murine T lymphocytes. J. Gen. Physiol., 1989, 93, 1061-1074.
53. Ying-Duo Gao, M.L.G. Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: Selectivity between voltage-gated and Maxi-K channels. Proteins Struct. Funct. Genet., 2003, 52, 146-154.
54. Grissmer, S.; Nguyen, A.N.; Aiyar, J.; Hanson, D.C.; Mather, R.J.; Gutman, G.A.; armilowicz, M.J.; Auperin, D.D.; Chandy, K.G. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol., 1994, 45, 1227-1234.
55. Beeton, C.; Pennington, M.W.; Wulff, H.; Singh, S.; Nugent, D.; Crossley, G.; Khaytin, I.; Calabresi, P.A.; Chen, C.-Y.; Gutman, G.A.; Chandy, K.G. Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol. Pharmacol., 2005, 67, 1369-1381.
56. Matheu, M.P.; Beeton, C.; Garcia, A.; Chi, V.; Rangaraju, S.; Safrina, O.; Monaghan, K.; Uemura, M.I.; Li, D.; Pal, S.; de la Maza, L.M.; Monuki, E.; Flugel, A.; Pennington, M.W.; Parker, I.; Chandy, K.G.; Cahalan, M.D. Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. Immunity, 2008, 29, 602-614.
57. Beeton, C.; Wulff, H.; Standifer, N.E.; Azam, P.; Mullen, K.M.; Pennington, M.W.; Kolski-Andreaco, A.; Wei, E.; Grino, A.; Counts, D.R.; Wang, P.H.; LeeHealey, C.J.; B, S.A.; Sankaranarayanan, A.; Homerick, D.; Roeck, W.W.; Tehranzadeh, J.; Stanhope, K.L.; Zimin, P.; Havel, P.J.; Griffey, S.; Knaus, H.G.; Nepom, G.T.; Gutman, G.A.; Calabresi, P.A.; Chandy, K.G. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 17414-17419.
58. Baell, J.B. Potassium channel blockers as immunosuppressants. Expert Opin. Ther. Patents, 2005, 15, 1209-1220.
59. Hill, R.J.; Grant, A.M.; Volberg, W.; Rapp, L.; Faltynek, C.; Miller, D.; Pagani, K.; Baizman, E.; Wang, S.; Guiles, J.W.; Krafte, D.S. WIN 17317-3: novel nonpeptide antagonist of voltage-activated K+ channels in human T lymphocytes. Mol. Pharmacol., 1995, 48, 98-104.
60. Nguyen, A.; Kath, J.C.; Hanson, D.C.; Biggers, M.S.; Canniff, P.C.; B., D.C.; J., M.R.; J., B.M.; Rauer, H.; Aiyar, J.; Lepple- Wienhues, A.; Gutman, G.A.; Grissmer, S.; Cahalan, M.D.; Chandy, K.G. Novel nonpeptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol. Pharmacol., 1996, 50, 1672-1679.
61. Wanner, S.G.; Glossmann, H.; Knaus, H.G.; Baker, R.; Parsons, W.; Rupprecht, K.M.; Brochu, R.; Cohen, C.J.; Schmalhofer, W.; Smith, M.; Warren, V.; Garcia, M.L.; Kaczorowski, G.J. WIN 17317-3, a new high-affinity probe for voltage-gated sodium channels. Biochemistry, 1999, 38, 11137-11146.
62. Felix, J.P.; Bugianesi, R.M.; Schmalhofer, W.A.; Borris, R.; Goetz, M.A.; Hensens, O.D.; Bao, J.M.; Kayser, F.; Parsons, W.H.; Rupprecht, K.; Garcia, M.L.; Kaczorowski, G.J.; Slaughter, R.S. Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3. Biochemistry, 1999, 38, 4922-4930.
63. Hanner, M.; Schmalhofer, W.A.; Green, B.; Bordallo, C.; Liu, J.; Slaughter, R.S.; Kaczorowski, G.J.; Garcia, M.L. Binding of correolide to K(v)1 family potassium channels. Mapping the domains of high affinity interaction. J. Biol. Chem., 1999, 274, 25237-25244.
64. Bao, J.; Miao, S.; Kayser, F.; Kotliar, A.J.; Baker, R.K.; Doss, G.A.; Felix, J. P.; Bugianesi, R.M.; Slaughter, R.S.; Kaczorowski, G.J.; Garcia, M.L.; Ha, S.N.; Castonguay, L.; Koo, G.C.; Shah, K.; Springer, M.S.; Staruch, M.J.; Parsons, W.H.; Rupprecht, K.M. Potent Kv1.3 inhibitors from correolide-modification of the C18 position. Bioorg. Med. Chem. Lett., 2005, 15, 447-451.
65. Miao, S.; Bao, J.; Garcia, M.L.; Goulet, J.L.; Hong, X.J.; Kaczorowski, G.J.; Kayser, F.; Koo, G.C.; Kotliar, A.; Schmalhofer, W.A.; Shah, K.; Sinclair, P.J.; Slaughter, R.S.; Springer, M.S.; Staruch, M.J.; Tsou, N.N.; Wong, F.; Parsons, W.H.; Rupprecht, K.M. Benzamide derivatives as blockers of Kv1.3 ion channel. Bioorg. Med. Chem. Lett., 2003, 13, 1161-1164.
66. Hanson, D.C.; Nguyen, A.; Mather, R.J.; Rauer, H.; Koch, K.; Burgess, L.E.; Rizzi, J. P.; Donovan, C.B.; Bruns, M.J.; Canniff, P.C.; Cunningham, A.C.; Verdries, K.A.; Mena, E.; Kath, J.C.; Gutman, G.A.; Cahalan, M.D.; Grissmer, S.; Chandy, K.G. UK- 78,282, a novel piperidine compound that potently blocks the Kv1.3 voltage-gated potassium channel and inhibits human T cell activation. Br. J. Pharmacol., 1999, 126, 1707-1716.
67. Burgess, L.E.; Koch, K.; Cooper, K.; Biggers, M.S.; Ramchandani, M.; Smitrovich, J.H.; Gilbert, E.J.; Bruns, M.J.; Mather, R.J.; Donovan, C.B.; Hanson, D.C. The SAR of UK-78,282: a novel blocker of human T cell Kv1.3 potassium channels. Bioorg. Med. Chem. Lett., 1997, 7, 1047-1052.
68. Lew, A.; Chamberlin, A.R. Blockers of human T cell Kv1.3 potassium channels using de novo ligand design and solid-phase parallel combinatorial chemistry. Bioorg. Med. Chem. Lett., 1999, 9, 3267-3272.
69. Hidalgo, P.; MacKinnon, R. Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor. Science, 1995, 268, 307-310.
70. Bohuslavizki, K.H.; Hänsel, W.; Kneip, A.; Koppenhöfer, E.; Niemöller, E.; Sanmann, K. Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases. Gen. Physiol. Biophys., 1994, 13, 309-328.
71. Vennekamp, J.; Wulff, H.; Beeton, C.; Calabresi, P. A.; Grissmer, S.; Hansel, W.; Chandy, K.G. Kv1.3-Blocking 5-Phenylalkoxypsoralens: A New Class of Immunomodulators. Mol. Pharmacol., 2004, 65, 1364-1374.
72. Schmitz, A.; Sankaranarayanan, A.; Azam, P.; Schmidt-Lassen, K.; Homerik, D.; Hansel, W.; Wulff, H. Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Mol. Pharmacol., 2005, 68, 1254-1270.
73. Azam, P.; Sankaranarayanan, A.; Homerick, D.; Griffey, S.; Wulff, H. Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis. J. Invest. Dermatol., 2007, 127, 1419-1429.
74. Baell, J.B.; Gable, R.W.; Harvey, A.J.; Nathan, T.; Herzog, T.; Hansel, W.; Wulff, H. Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: Synthesis and immunosuppressive activity. J. Med. Chem., 2004, 47, 2326-2336.
75. Harvey, A.J.; Baell, J.B.; Toovey, N.; Homerick, D.; Wulff, H. A new class of blockers of the voltage-gated potassium channel Kv1.3 via modification of the 4- or 7-position of hellinone. J. Med. Chem., 2006, 49, 1433-1441.
76. Flynn, B.; Baell, J.B.; Harvey, A.J.; Chaplin, J.H.; Paul, D.; Mould, J.A. Novel benzofuran potassium channel blockers and uses thereof. WO/2008/040057, 2008.
77. Flynn, B.; Baell, J.B.; Harvey, A.J.; Chaplin, J.H.; Paul, D.; Mould, J.A. Novel chromenone potassium channel blockers and uses thereof. WO/2008/040058, 2008.
78. Flynn, B.L.; Baell, J.B.; Chaplin, J.H.; Gill, G.S.; Grobelny, D.W.; Harvey, A.J.; Mould, J.A.; Paul, D. Novel aryl potassium channel blockers and uses thereof. WO/2009/043117, 2009.
79. http://www.bionomics.com.au/page.php?section=105 Accessed October 2009.
80. Ford, J.; Madge, D.J.; Payne, H.J.; Knight, J.D. Thieno(3,2- c)pyridine compounds. WO/2007/066127, 2007.
81. Horiuchi, H. Recent advance in antiplatelet therapy: The mechanisms, evidence and approach to the problems. Ann. Med., 2006, 38, 162-172.
82. Gradl, S.N.; Felix, J.P.; Isacoff, E.Y.; Garcia, M.L.; Trauner, D. Protein surface recognition by rational design: nanomolar ligands for potassium channels. J. Am. Chem. Soc., 2003, 125, 12668-12669.
83. Ader, C.; Schneider, R.; Hornig, S.; Velisetty, P.; Wilson, E.M.; Lange, A.; Giller, K.; Ohmert, I.; Martin-Eauclaire, M.F.; Trauner, D.; Becker, S.; Pongs, O.; Baldus, M. A structural link between inactivation and block of a K+ channel. Nat. Struct. Mol. Biol., 2008, 15, 605-612.
84. Pegoraro, S.; Lang, M.; Dreker, T.; Kraus, J.; Hamm, S.; Meere, C.; Feurle, J.; Tasler, S.; Prutting, S.; Kuras, Z.; Visan, V.; Grissmer, S. Inhibitors of potassium channels Kv1.3 and IK-1 as immunosuppressants. Bioorg. Med. Chem. Lett., 2009, 19, 2299-2304.
85. Piamphongsant, T.; Chuaprapaisilp, T. Treatment of pustular psoriasis with clofazimine. Br. J. Dermatol., 1978, 99, 303-305.
86. Ren, Y.R.; Pan, F.; Parvez, S.; Fleig, A.; Chong, C.R.; Xu, J.; Dang, Y.; Zhang, J.; Jiang, H.; Penner, R.; Liu, J.O. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes. PLoS ONE, 2008, 3, e4009.
87. Lanier, E.W. Diphenoxylate therapy for psoriasis. Arch. Dermatol., 1985, 121, 1486.
88. Lanier, E.W. Basic diphenoxylate therapy. Arch. Dermatol., 1986, 122, 382.
89. Lanier, E.W. Method for treatment of various dermatological conditions. US 4,383,000, 1983.
90. Grissmer, S.; Dethlefs, B.; Wasmuth, J.J.; Goldin, A.L.; Gutman, G.A.; Cahalan, M.D.; Chandy, K.G. Expression and chromosomal localization of a lymphocyte K+ channel gene. Proc. Natl. Acad. Sci. U. S. A., 1990, 87, 9411-9415.
91. Lu, G.W.; Flynn, G.L. In Modern Pharmaceutics, Applications and Advances; Florence, A.T., Siepmann, J., Ed.; Informa Healthcare: New York, 2009; pp. 43-100.
92. Finnin, B.C.; Morgan, T.M. Transdermal penetration enhancers: applications, limitations, and potential. J. Pharm. Sci., 1999, 88, 955-958.
93. Cross, S.E.; Magnusson, B.M.; Winckle, G.; Anissimov, Y.; Roberts, M.S. Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers. J. Invest. Dermatol., 2003, 120, 759-764.
94. Saini, L.; Gupta, S.P.; Kumar Satluri, V.S. A QSAR study on some series of sodium and potassium channel blockers. Med. Chem., 2009, 5, 570-576.
95. Zhou, Y.; Morais-Cabral, J.H.; Kaufman, A.; MacKinnon, R. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. Nature, 2001, 414, 4348.
96. Long, S.B.; Campbell, E.B.; Mackinnon, R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science, 2005, 309, 897-903.
97. Long, S.B.; Tao, X.; Campbell, E.B.; MacKinnon, R. Atomic structure of a voltage-dependent K+ channel in a lipid membranelike environment. Nature, 2007, 450, 376-382.
98. MacKinnon, R.; Miller, C. Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science, 1989, 245, 1382-1385.
99. MacKinnon, R.; Heginbotham, L.; Abramson, T. Mapping the receptor site for charybdotoxin, a pore-blocking potassium channel inhibitor. Neuron, 1990, 5, 767-771.
100. Chandy, K.G.; Cahalan, M.; Pennington, M.; Norton, R.S.; Wulff, H.; Gutman, G.A. Potassium channels in T lymphocytes: toxins to therapeutic immunosuppressants. Toxicon, 2001, 39, 1269-1276.
101. Phillips, L.R.; Milescu, M.; Li-Smerin, Y.; Mindell, J.A.; Kim, J.I.; Swartz, K.J. Voltage-sensor activation with a tarantula toxin as cargo. Nature, 2005, 436, 857-860.
102. Lee, S.Y.; MacKinnon, R. A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature, 2004, 430, 232-235.
103. Hanner, M.; Green, B.; Gao, Y.D.; Schmalhofer, W.A.; Matyskiela, M.; Durand, D.J.; Felix, J.P.; Linde, A.R.; Bordallo, C.; Kaczorowski, G.J.; Kohler, M.; Garcia, M.L. Binding of correolide to the K(v)1.3 potassium channel: characterization of the binding domain by site-directed mutagenesis. Biochemistry, 2001, 40, 11687-11697.
104. Bruhova, I.; Zhorov, B.S. Monte Carlo-energy minimization of correolide in the Kv1.3 channel: possible role of potassium ion in ligand-receptor interactions. BMC Struct. Biol., 2007, 7, 5.
105. Wuttke, T.V.; Seebohm, G.; Bail, S.; Maljevic, S.; Lerche, H. The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol. Pharmacol., 2005, 67, 1009-1017.
106. Zhang, Z.H.; Rhodes, K.J.; Childers, W.E.; Argentieri, T.M.; Wang, Q. Disinactivation of N-type inactivation of voltage-gated K channels by an erbstatin analogue. J. Biol. Chem., 2004, 279, 29226-29230.
107. Lu, Q.; Peevey, J.; Jow, F.; Monaghan, M.M.; Mendoza, G.; Zhang, H.; Wu, J.; Kim, C.Y.; Bicksler, J.; Greenblatt, L.; Lin, S.S.; Childers, W.; Bowlby, M.R. Disruption of Kv1.1 N-type inactivation by novel small molecule inhibitors (disinactivators). Bioorg. Med. Chem., 2008, 16, 3067-3075.
108. Kopljar, I.; Labro, A.J.; Cuypers, E.; Johnson, H.W.; Rainier, J.D.; Tytgat, J.; Snyders, D.J. A polyether biotoxin binding site on the lipid-exposed face of the pore domain of Kv channels revealed by the marine toxin gambierol. Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 9896-9901.
109. Matheu, M.P.; Beeton, C.; Garcia, A.; Chi, V.; Rangaraju, S.; Safrina, O.; Monaghan, K.; Uemura, M.I.; Li, D.; Pal, S.; de la Maza, L.M.; Monuki, E.; Flugel, A.; Pennington, M.W.; Parker, I.; Chandy, K.G.; Cahalan, M.D. Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. Immunity, 2008, 29, 602-614.