scholarly journals Identification and optimization of 2-aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels

2015 ◽  
Vol 172 (14) ◽  
pp. 3495-3509 ◽  
Author(s):  
Yingmin Zhu ◽  
Yungang Lu ◽  
Chunrong Qu ◽  
Melissa Miller ◽  
Jinbin Tian ◽  
...  
Keyword(s):  
Trpc5 Channels

scholarly journals Critical Role of Pertussis Toxin Sensitive G Proteins in the Activation of TRPC4 and TRPC5 Channels

2010 ◽  
Vol 98 (3) ◽  
pp. 326a-327a
Author(s):  
Rui Xiao ◽  
Jinbin Tian ◽  
Jisen Tang ◽  
Alexander V. Zholos ◽  
Michael X. Zhu
Keyword(s):  
G Proteins ◽  
Pertussis Toxin ◽  
Critical Role ◽  
Trpc5 Channels

scholarly journals TRPC5 Channels are Inhibited by Wt Presenilin1 but not the Alzheimer's Disease Mutant M146V

2017 ◽  
Vol 112 (3) ◽  
pp. 406a
Author(s):  
Sukhjinder Kaur ◽  
Zuleen Chia-Chang ◽  
Paris Hanson ◽  
Laura Yorke ◽  
Zafir Buraei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Trpc5 Channels

Effect of non-steroidal anti-inflammatory drugs and new fenamate analogues on TRPC4 and TRPC5 channels

2012 ◽  
Vol 83 (7) ◽  
pp. 923-931 ◽  
Author(s):  
Hongni Jiang ◽  
Bo Zeng ◽  
Gui-Lan Chen ◽  
David Bot ◽  
Sarah Eastmond ◽  
...  
Keyword(s):  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Trpc5 Channels

scholarly journals Xanthine-Based Photoaffinity Probes Allow Assessment of Ligand Engagement by TRPC5 Channels

2020 ◽  
Author(s):  
Claudia Bauer ◽  
Aisling Minard ◽  
Isabelle Pickles ◽  
Matthew Burnham ◽  
Nikil Kapur ◽  
...  
Keyword(s):  
Small Molecule ◽  
Drug Targets ◽  
Direct Evidence ◽  
Binding Mode ◽  
Chemical Probes ◽  
Binding Interaction ◽  
Biological Studies ◽  
Photoaffinity Probes ◽  
Direct Binding ◽  
Trpc5 Channels

TRPC1/4/5 cation channels are emerging drug targets for the treatment of, amongst others, central nervous system (CNS) disorders, kidney disease, and cardiovascular and metabolic disease. Various small-molecule TRPC1/4/5 modulators have been reported, including highly potent xanthine derivatives that can distinguish between specific TRPC1/4/5 tetramers. However, there is a paucity of information about their binding mode, which limits the ability to develop them further as chemical probes of specific TRPC1/4/5 channels for use in fundamental biological studies and drug discovery programmes. Here, we report the development of a set of potent xanthine-based photoaffinity probes that functionally mimic the xanthines Pico145 and AM237, respectively. Using these probes, we have developed a quantitative photoaffinity labelling protocol for TRPC5 channels. Our results provide the first direct evidence that xanthines modulate TRPC5 channels through a direct binding interaction with TRPC5 protein, and the first quantitative method for the assessment of binding interactions of TRPC5 and small molecules. Our method may allow the study of the mode-of-action of other TRPC1/4/5 modulators, and the identification of small molecule binding sites of TRPC1/4/5 channels.

scholarly journals Potent, selective, and subunit‐dependent activation of TRPC5 channels by a xanthine derivative

2019 ◽  
Vol 176 (20) ◽  
pp. 3924-3938 ◽  
Author(s):  
Aisling Minard ◽  
Claudia C. Bauer ◽  
Eulashini Chuntharpursat‐Bon ◽  
Isabelle B. Pickles ◽  
David J. Wright ◽  
...  
Keyword(s):  
Xanthine Derivative ◽  
Trpc5 Channels

scholarly journals Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth

2006 ◽  
Vol 572 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Hui Hui ◽  
Damian McHugh ◽  
Meredith Hannan ◽  
Fanning Zeng ◽  
Shang-Zhong Xu ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Sensing Mechanism ◽  
Calcium Sensing ◽  
Trpc5 Channels

scholarly journals TRPC5 channels undergo changes in gating properties during the activation-deactivation cycle

2008 ◽  
Vol 216 (1) ◽  
pp. 162-171 ◽  
Author(s):  
Alexander G. Obukhov ◽  
Martha C. Nowycky
Keyword(s):  
Trpc5 Channels

scholarly journals Selective Gαi Subunits as Novel Direct Activators of Transient Receptor Potential Canonical (TRPC)4 and TRPC5 Channels

2012 ◽  
Vol 287 (21) ◽  
pp. 17029-17039 ◽  
Author(s):  
Jae-Pyo Jeon ◽  
Chansik Hong ◽  
Eun Jung Park ◽  
Ju-Hong Jeon ◽  
Nam-Hyuk Cho ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor ◽  
Trpc5 Channels

scholarly journals Xanthine-Based Photoaffinity Probes Allow Assessment of Ligand Engagement by TRPC5 Channels

2020 ◽  
Author(s):  
Claudia Bauer ◽  
Aisling Minard ◽  
Isabelle Pickles ◽  
Matthew Burnham ◽  
Nikil Kapur ◽  
...  
Keyword(s):  
Small Molecule ◽  
Drug Targets ◽  
Direct Evidence ◽  
Binding Mode ◽  
Chemical Probes ◽  
Binding Interaction ◽  
Biological Studies ◽  
Photoaffinity Probes ◽  
Direct Binding ◽  
Trpc5 Channels

TRPC1/4/5 cation channels are emerging drug targets for the treatment of, amongst others, central nervous system (CNS) disorders, kidney disease, and cardiovascular and metabolic disease. Various small-molecule TRPC1/4/5 modulators have been reported, including highly potent xanthine derivatives that can distinguish between specific TRPC1/4/5 tetramers. However, there is a paucity of information about their binding mode, which limits the ability to develop them further as chemical probes of specific TRPC1/4/5 channels for use in fundamental biological studies and drug discovery programmes. Here, we report the development of a set of potent xanthine-based photoaffinity probes that functionally mimic the xanthines Pico145 and AM237, respectively. Using these probes, we have developed a quantitative photoaffinity labelling protocol for TRPC5 channels. Our results provide the first direct evidence that xanthines modulate TRPC5 channels through a direct binding interaction with TRPC5 protein, and the first quantitative method for the assessment of binding interactions of TRPC5 and small molecules. Our method may allow the study of the mode-of-action of other TRPC1/4/5 modulators, and the identification of small molecule binding sites of TRPC1/4/5 channels.

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