Article
Pharmacology & Pharmacy
Xiao-Yu Cheng, Shu-Fang Li, Yong Chen, Ying-Jie Zhao, Wei Hu, Chao Lu, Ren-Peng Zhou
Summary: TRPM7 is a channel protein located on the cell membrane that regulates the balance of intracellular Mg2+. It plays an important role in cell proliferation, adhesion, migration, and is directly related to disease occurrence and development.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Yuan-Yuan Gao, Wen Tian, Hui-Nan Zhang, Yang Sun, Jing-Ru Meng, Wei Cao, Xiao-Qiang Li
Summary: TRPCs channels play crucial roles in human physiological and pathological processes, but finding selective TRPCs modulators remains challenging. Further exploration for more effective and selective TRPCs modulators is needed.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Review
Cell Biology
Bethan A. Cole, Esther B. E. Becker
Summary: The TRPC3 channel is a crucial player in calcium signaling and is regulated by various endogenous and exogenous factors. Recent studies have advanced our understanding of the regulatory mechanisms of TRPC3, which has implications for the development of therapeutic interventions for diseases associated with this channel.
Review
Chemistry, Medicinal
Zelin Hu, Ya Zhang, Wenhan Yu, Junjie Li, Jiaqi Yao, Jifa Zhang, Jiaxing Wang, Chengdi Wang
Summary: The TRPA1 channel is a non-selective cation channel that detects irritant chemicals and is associated with pain, inflammation, and pruritus. TRPA1 antagonists have shown promise as treatments for various diseases, but their performance in clinical studies has been disappointing. There is a need for antagonists with higher selectivity, metabolic stability, and solubility. Additionally, TRPA1 agonists help in understanding activation mechanisms and aid in the screening of antagonists. This perspective summarizes the recent development of TRPA1 antagonists and agonists, focusing on structure-activity relationships and pharmacological activity, with the aim of inspiring the development of more effective TRPA1-modulating drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Omar Mahmoud, Georgia Biazus Soares, Gil Yosipovitch
Summary: Transient Receptor Potential (TRP) channels, found abundantly in the skin, play a crucial role in the sensory pathways of itch, pain, and inflammation. This review article explores the complex physiology of different TRP channels and their involvement in modulating itch sensation and the pathophysiology of acute and chronic itch conditions. The article also highlights emerging small molecule and topical TRP channel agents as potential anti-pruritic treatments, with some advancing into clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Katelyn E. Sadler, Francie Moehring, Stephanie Shiers, Lauren J. Laskowski, Alexander R. Mikesell, Zakary R. Plautz, Allison N. Brezinski, Christina M. Mecca, Gregory Dussor, Theodore J. Price, John D. McCorvy, Cheryl L. Stucky
Summary: The study identified TRPC5 as a key contributor to tactile and spontaneous pain in multiple rodent pain models, particularly in conditions characterized by elevated LPC concentrations. 75% of human sensory neurons express TRPC5, and its activity is directly modulated by LPC.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Meiling Shen, Lingfeng Li, Yue Li, Xi Gu, Longhui Bai, Chengfeng Xia, Wenyong Xiong, Zhili Zuo
Summary: This study conducted virtual screening of over 1.5 million molecules from the Chemdiv database to identify potential inhibitors of hTRPC5. The screening process evaluated the affinities of the candidates and assessed their inhibitory effects on Ca2+ influx. Two molecules, SML-1 and SML-13, showed significant inhibition of intracellular Ca2+ levels and could potentially be lead compounds for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Mengkang Gao, Yusui Wang, Lanqi Liu, Zhenrui Qiao, Lin Yan
Summary: TRPV1 is a nonselective cation channel widely expressed in the CNS and PNS. Research on TRPV1 regulators has been ongoing for over 20 years, focusing on developing new drugs for pain management. Despite challenges, TRPV1 modulators remain promising therapeutic agents for pain relief.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2021)
Article
Chemistry, Medicinal
Yin-Ying Mak, Bi-Juin Loong, Paul Millns, Claudia C. Bauer, Robin S. Bon, Yvonne Mbaki, Fong-Kai Lee, Kuan-Hon Lim, Cin Kong, Sue-Mian Then, Kang-Nee Ting
Summary: This study investigated the vasorelaxant effects of schwarzinicine A, a newly reported alkaloid from Ficus schwarzii Koord. The results showed that schwarzinicine A exerts its significant vasorelaxant effect by blocking multiple TRPC channels and L-type VGCC.
PHYTOTHERAPY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Bei Miao, Yue Yin, Guangtong Mao, Benhuo Zhao, Jiaojiao Wu, Hengliang Shi, Sujuan Fei
Summary: This study revealed the involvement of BDNF in driving mechanical allodynia in diabetic neuropathy pain rats through the activation of the TRPC6 channel. Inhibiting TRPC6 can alleviate BDNF-induced mechanical allodynia, offering a potential novel strategy for the management of diabetic neuropathy pain.
Article
Oncology
Li-ping Bai, Ya-li Chen, Ai Zheng
Summary: This study found that the high expression of TRPC6 protein in cervical cancer cell lines HeLa and SiHa may be related to the malignant behavior of the cells. SKF-96365 inhibits cell proliferation and DNA synthesis, while OAG promotes cell proliferation and DNA synthesis.
CANCER CELL INTERNATIONAL
(2022)
Review
Medicine, Research & Experimental
Fangyan Hu, Xiaohua Song, Dingxin Long
Summary: Calcium is a crucial signaling molecule in all cells, with TRPA1 being a potential target for treating sensory disorders such as pain and pruritus. TRPA1 is the only identified member of the ankyrin subfamily in mammals and has high permeability to calcium ions.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Xin Wen, Yidi Peng, Mengru Gao, Yuzhong Zhu, Yifei Zhu, Fan Yu, Tingting Zhou, Jing Shao, Lei Feng, Xin Ma
Summary: This study demonstrates that TRPC1 improves cardiac function after myocardial infarction by promoting angiogenesis. The study explores the regulatory mechanisms of HIF-1 alpha and MEK/ERK, and finds that treatment with dimethyloxaloylglycine has a protective effect on myocardial infarction.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Biochemistry & Molecular Biology
Anna Luo, Aili Wang, Peter Muiruri Kamau, Ren Lai, Lei Luo
Summary: Centipedes are ancient and successful venomous animals, with their venoms targeting ion channels in the nervous system. Understanding the mechanism of neurotoxins acting on ion channels contributes to the knowledge of centipede venoms and channel functions. The unique structure and selective activities of centipede venom peptides make them potential research tools and biological drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mehek Ningoo, Leigh D. Plant, Anna Greka, Diomedes E. Logothetis
Summary: TRPC5 ion channels, expressed in the brain and kidney, are promising therapeutic targets for diseases like focal segmental glomerular sclerosis. The role of PIP2 in controlling TRPC5 channel activity through gating rather than cell surface density, influenced by DAG and lanthanide ions, provides new opportunities for targeted therapies in chronic kidney diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Christopher D. Aretz, Anish K. Vadukoot, Corey R. Hopkins
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Review
Pharmacology & Pharmacy
Siddharth S. Kesharwani, Pooja Mallya, Vadikari Arun Kumar, Vikas Jain, Swagat Sharma, Surajit Dey
Article
Biochemistry & Molecular Biology
Maria E. Burkovetskaya, Qiaoling Liu, Anish K. Vadukoot, Nagsen Gautam, Yazen Alnouti, Sushil Kumar, Klaus Miczek, Shilpa Buch, Corey R. Hopkins, Minglei Guo
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Chemistry, Medicinal
Darren W. Engers, Sean R. Bollinger, Andrew S. Felts, Anish K. Vadukoot, Charles H. Williams, Anna L. Blobaum, Craig W. Lindsley, Charles C. Hong, Corey R. Hopkins
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Medicinal
Christopher D. Aretz, Sujay V. Kharade, Keagan Chronister, Renata Rusconi Trigueros, Erick J. Martinez Rodriguez, Peter M. Piermarini, Jerod S. Denton, Corey R. Hopkins
Summary: Zika virus, dengue fever, and chikungunya are arboviruses spread by infected Aedes aegypti mosquitoes. Current control strategies rely on using insecticides to prevent mosquito bites, but increasing resistance complicates control efforts. Inhibiting the Kir channel of Aedes aegypti has shown promise for developing novel mosquitocides.
Article
Oncology
Balawant Kumar, Rizwan Ahmad, Swagat Sharma, Saiprasad Gowrikumar, Mark Primeaux, Sandeep Rana, Amarnath Natarajan, David Oupicky, Corey R. Hopkins, Punita Dhawan, Amar B. Singh
Summary: Colorectal cancer (CRC) therapy faces challenges due to cancer stem cells (CSCs) resistance to chemotherapy. Inhibiting autophagy with 36-077, a potent PIK3C3/VPS34 inhibitor, shows promise in improving the efficacy of CRC therapy by targeting CSCs.
Article
Biochemistry & Molecular Biology
Suliman Almahmoud, Catherine C. Elix, Jeremy O. Jones, Corey R. Hopkins, Jonathan L. Vennerstrom, Haizhen A. Zhong
Summary: The PPAR gamma antagonist is crucial for inhibiting prostate cancer cell growth, and residues Arg288, Lys367, and His449 are important for PPAR gamma antagonist binding.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Viktoriya Mashinson, Corey R Hopkins
Summary: Mosquitoes remain the most lethal animals to humans due to the diseases they carry, but resistance to commonly used neurotoxic insecticides has emerged, impacting the efficacy of chemical control agents and beneficial insects such as honeybees. Developing new mosquitocides with novel mechanisms of action is urgently needed, and this review discusses efforts targeting the renal inward rectifier potassium channel (Kir) of mosquitoes in this regard.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Swagat Sharma, Juan L. Pablo, Kirsten T. Tolentino, Wacey Gallegos, Jennifer Hinman, Madison Beninato, MacKenzie Asche, Anna Greka, Corey R. Hopkins
Summary: The transient receptor potential cation channel 5 (TRPC5) is a crucial player in various cellular processes and has gained attention as a potential therapeutic target. Recent studies highlight its involvement in regulating podocyte survival, suggesting a potential treatment for chronic kidney disease, while inhibition of TRPC5 is proposed as an effective approach for alleviating spontaneous and tactile pain. This report presents the discovery of 16 f as a potent and selective TRPC5 inhibitor through further exploration of the 2-aminobenzimidazole scaffold.
Article
Chemistry, Medicinal
Swagat Sharma, Qi Peng, Anish K. Vadukoot, Christopher D. Aretz, Aaron A. Jensen, Alexander Wallick, Xinzhong Dong, Corey R. Hopkins
Summary: This study describes the discovery and characterization of a series of 2-sulfonamidebenzamides as allosteric modulators of MrgX1, a potential nonopioid receptor for chronic pain treatment. The research successfully improved the potency of MrgX1 and identified key compounds with improved stability.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Abigail N. Smith, Madelaine P. Thorpe, Daniel J. Blackwell, Suzanne M. Batiste, Corey R. Hopkins, Nathan D. Schley, Bjorn C. Knollmann, Jeffrey N. Johnston
Summary: The synthesis of N-Me and N-H analogues of ent-verticilide was described to enable a structure-activity relationship study based on cardiac ryanodine receptor (RyR2) calcium ion channel inhibition. The study found that a high degree of N-methyl amide content is critical for activity in the ent-verticilide series but not entirely so for the ent-verticilide B1 series.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Viktoriya Mashinson, Thomas M. Webster, Anish K. Vadukoot, Kirsten T. Tolentino, Princess Simeon, Iram Fatima, Punita Dhawan, Corey R. Hopkins
Summary: Colorectal cancer is a major cause of cancer-related deaths worldwide, and metastasis is a significant challenge in its treatment. The overexpression of claudin-1 in colorectal cancer is associated with poor prognosis, and inhibiting claudin-1 may have therapeutic potential. In this study, researchers identified a small molecule that inhibits claudin-1 dependent colorectal cancer progression and discovered a new compound with enhanced potency in SW620 cells through lead optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Swagat Sharma, Lauren Lesiak, Christopher D. Aretz, Yu Du, Sushil Kumar, Nagsen Gautam, Yazen Alnouti, Nikilesh Dhuria, Yashpal S. Chhonker, C. David Weaver, Corey R. Hopkins
Summary: The study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as GIRK channel activators. These compounds show potent and selective activation of GIRK1/2 with improved metabolic stability compared to urea-based compounds.
RSC MEDICINAL CHEMISTRY
(2021)
