Use of Kv1.3 Blockers for Inflammatory Skin Conditions

被引：16

作者：

Nguyen, W. ^{[1
]}

Howard, B. L. ^{[1
]}

Neale, D. S. ^{[1
]}

Thompson, P. E. ^{[1
]}

White, P. J. ^{[1
]}

Wulff, H. ^{[2
]}

Manallack, D. T. ^{[1
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

[2] Univ Calif Davis, Dept Pharmacol, Genome & Biomed Sci Facil, Davis, CA 95616 USA

来源：

CURRENT MEDICINAL CHEMISTRY | 2010年 / 17卷 / 26期

关键词：

Psoriasis; Kv1.3; channel; inflammation; drug design; autoimmune disorder; MEMORY T-CELLS; GATED POTASSIUM CHANNEL; CHRONIC PLAQUE PSORIASIS; N-TYPE INACTIVATION; K+ CHANNEL; AUTOIMMUNE-DISEASES; MULTIPLE-SCLEROSIS; PEPTIDE INHIBITOR; DIPHENOXYLATE THERAPY; ION CHANNELS;

D O I：

10.2174/092986710792065072

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent results using animal models of inflammatory skin conditions have shown that blockers of the voltage-gated potassium channel, Kv1.3 hold great promise for clinical utility. Kv1.3 blockers act as immunosuppressants by modulating the various subsets of inflammatory T and B cells involved in autoimmune disorders. While peptidic inhibitors based on naturally occurring venoms demonstrate potent and selective Kv1.3 blockade, these require parenteral administration and may face potential immunogenicity problems. Small molecule blockers show considerable diversity, however selectivity over other Kv1-family channels has been difficult to achieve. More recent advances have added to the evidence that Kv1.3 channels are a suitable therapeutic target and that the development of novel and selective agents will herald new drugs for inflammatory skin disorders.

引用

页码：2882 / 2896

页数：15

共 104 条

[1] A structural link between inactivation and block of a K+ channel [J].

Ader, Christian ;

Schneider, Robert ;

Hornig, Soenke ;

Velisetty, Phanindra ;

Wilson, Erica M. ;

Lange, Adam ;

Giller, Karin ;

Ohmert, Iris ;

Martin-Eauclaire, Marie-France ;

Trauner, Dirk ;

Becker, Stefan ;

Pongs, Olaf ;

Baldus, Marc .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2008, 15 (06) :605-612

[2] The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-γ, interleukin-2, and tumor necrosis factor-α, 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].

Austin, LM ;

Ozawa, M ;

Kikuchi, T ;

Walters, IB ;

Krueger, JG .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 113 (05) :752-759

[3] Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis [J].

Azam, Philippe ;

Sankaranarayanan, Ananthakrishnan ;

Homerick, Daniel ;

Griffey, Stephen ;

Wulff, Heike .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (06) :1419-1429

[4] The new paradigm of T-cell homeostatic proliferation-induced autoimmunity [J].

Baccala, R ;

Theofilopoulos, AN .

TRENDS IN IMMUNOLOGY, 2005, 26 (01) :5-8

[5] Potassium channel blockers as immunosuppressants [J].

Baell, JB .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (09) :1209-1220

[6] Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3:: Synthesis and immunosuppressive activity [J].

Baell, JB ;

Gable, RW ;

Harvey, AJ ;

Toovey, N ;

Herzog, T ;

Hänsel, W ;

Wulff, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (09) :2326-2336

[7] Potent Kv1.3 inhibitors from correolide - modification of the C18 position [J].

Bao, JM ;

Miao, SW ;

Kayser, F ;

Kotliar, AJ ;

Baker, RK ;

Dossa, GA ;

Felix, JP ;

Bugianesi, RM ;

Slaughter, RS ;

Kaczorowski, GJ ;

Garcia, ML ;

Ha, SN ;

Castonguay, L ;

Koo, GC ;

Shah, K ;

Springer, MS ;

Staruch, MJ ;

Parsons, WH ;

Rupprecht, KM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (02) :447-451

[8] Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases [J].

Beeton, C ;

Pennington, MW ;

Wulff, H ;

Singh, S ;

Nugent, D ;

Crossley, G ;

Khaytin, I ;

Calabresi, PA ;

Chen, CY ;

Gutman, GA ;

Chandy, KG .

MOLECULAR PHARMACOLOGY, 2005, 67 (04) :1369-1381

[9] Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases [J].

Beeton, Christine ;

Wulff, Heike ;

Standifer, Nathan E. ;

Azam, Philippe ;

Mullen, Katherine M. ;

Pennington, Michael W. ;

Kolski-Andreaco, Aaron ;

Wei, Eric ;

Grino, Alexandra ;

Counts, Debra R. ;

Wang, Ping H. ;

LeeHealey, Christine J. ;

Andrews, Brian S. ;

Sankaranarayanan, Ananthakrishnan ;

Homerick, Daniel ;

Roeck, Werner W. ;

Tehranzadeh, Jamshid ;

Stanhope, Kimber L. ;

Zimin, Pavel ;

Havel, Peter J. ;

Griffey, Stephen ;

Knaus, Hans-Guenther ;

Nepom, Gerald T. ;

Gutman, George A. ;

Calabresi, Peter A. ;

Chandy, K. George .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (46) :17414-17419

[10]

Bionomics Ltd, 2009, Patent No. [WO2009043117, 2009043117]

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