Plant K+ channels: structure, activity and function

1996 ◽  
Vol 24 (4) ◽  
pp. 964-971 ◽  
Author(s):  
I. Chérel ◽  
P. Daram ◽  
F. Gaymard ◽  
C. Horeau ◽  
J.-B. Thibaud ◽  
...  
Keyword(s):  
K Channels ◽  
Structure Activity ◽  
And Function

scholarly journals Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suxing Liu ◽  
Dong Liu ◽  
Ru Shen ◽  
Di Li ◽  
Qiyue Hu ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Clinical Success ◽  
Systemic Exposure ◽  
Skin Inflammation ◽  
Targeted Therapeutics ◽  
High Exposure ◽  
Structure Activity ◽  
Potential Safety ◽  
Systematic Structure ◽  
And Function

AbstractClinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest. Systematic structure activity relationship study and multi-parameter optimization led to the discovery of a novel RORγ antagonist (SHR168442) with desired properties for a topical drug. It suppressed the transcription of IL-17 gene, leading to reduction of IL-17 cytokine secretion. It showed high exposure in skin, but low in plasma. Topical application of SHR168442 in Vaseline exhibited excellent efficacy in the imiquimod-induced and IL-23-induced psoriasis-like skin inflammation mouse models and correlated with the reduction of Th17 pathway cytokines, IL-6, TNFα and IL-17A. This work demonstrated restricted skin exposure of RORγ antagonist may provide a new topical treatment option as targeted therapeutics for mild to moderate psoriasis patients and may be suitable for the treatment of any other inflammatory disorders that are accessible locally.

scholarly journals Minimal art: Or why small viral K+ channels are good tools for understanding basic structure and function relations

2011 ◽  
Vol 1808 (2) ◽  
pp. 580-588 ◽  
Author(s):  
Gerhard Thiel ◽  
Dirk Baumeister ◽  
Indra Schroeder ◽  
Stefan M. Kast ◽  
James L. Van Etten ◽  
...  
Keyword(s):  
Basic Structure ◽  
Structure And Function ◽  
K Channels ◽  
Minimal Art ◽  
And Function

Structure and function of two-pore-domain K channels: contributions from genetic model organisms

2005 ◽  
Vol 26 (7) ◽  
pp. 361-367 ◽  
Author(s):  
S BUCKINGHAM ◽  
J KIDD ◽  
R LAW ◽  
C FRANKS ◽  
D SATTELLE
Keyword(s):  
Genetic Model ◽  
Structure And Function ◽  
Model Organisms ◽  
K Channels ◽  
And Function ◽  
Pore Domain

scholarly journals Expression and Function of Endothelial Ca2+-Activated K+Channels in Human Mesenteric Artery

2000 ◽  
Vol 87 (6) ◽  
pp. 496-503 ◽  
Author(s):  
Ralf Köhler ◽  
Christiane Degenhardt ◽  
Meike Kühn ◽  
Norbert Runkel ◽  
Martin Paul ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
K Channels ◽  
And Function

scholarly journals Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68052 ◽  
Author(s):  
Kiril L. Hristov ◽  
Serge A. Y. Afeli ◽  
Shankar P. Parajuli ◽  
Qiuping Cheng ◽  
Eric S. Rovner ◽  
...  
Keyword(s):  
Detrusor Overactivity ◽  
Neurogenic Detrusor Overactivity ◽  
K Channels ◽  
And Function
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