Ion Channels as Therapeutic Drug Targets

2021 ◽  
pp. 1-28
Author(s):  
Maria L. Garcia ◽  
Gregory J. Kaczorowski
Keyword(s):  
Ion Channels ◽  
Drug Targets ◽  
Therapeutic Drug

scholarly journals A Short Guide to Electrophysiology and Ion Channels

2017 ◽  
Vol 20 ◽  
pp. 48 ◽  
Author(s):  
Hussein Nori Rubaiy
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Drug Targets ◽  
Neurological Diseases ◽  
Ionic Currents ◽  
Therapeutic Drug ◽  
Molecular Physiology ◽  
Patch Clamp Technique ◽  
Automated Technique ◽  
Electrophysiological Technique

The birth and discovery of electrophysiological science took place in the 18­­th century laying the path for our understanding of nerve membrane ionic currents. The pore-forming proteins, ion channels, are involved and play critical roles in very important physiological and pathological processes, such as neuronal signaling and cardiac excitability, therefore, they serve as therapeutic drug targets. The study of physiological, pharmacological and biophysical properties of ion channels can be done by patch clamp, a gold standard and powerful electrophysiological technique. The current review, in addition to highlight and cover the history of electrophysiology, patch clamp (conventional and automated) technique, and different types of ion channels, will also discuss the importance of ion channels in different neurological diseases and disorders. As the field of neuroscience is growing, this manuscript is intended as a guide to help in understanding the importance of ion channels, particularly in neuroscience, and also in using the patch clamp technique for the study of molecular physiology, pathophysiology, and pharmacology of neuronal ion channels. Importantly, this review will spotlight on the therapeutic aspect of neuronal ion channels.     This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals HMGA proteins as therapeutic drug targets: interaction of DNA with human HMGA1a

2009 ◽  
Vol 25 ◽  
pp. S6
Author(s):  
N. Saperas ◽  
R. Sánchez-Giraldo ◽  
E. Fonfría-Subirós ◽  
G. Sanahuja ◽  
M. Pagán ◽  
...  
Keyword(s):  
Drug Targets ◽  
Therapeutic Drug

Potential Drug Target Identification in Porphyromonas gingivalis using In-silico Subtractive Metabolic Pathway Analysis

2021 ◽  
Vol 20 (4) ◽  
pp. 887-896
Author(s):  
Prachi Sao ◽  
Yamini Chand ◽  
Atul Kumar ◽  
Sachidanand Singh
Keyword(s):  
Porphyromonas Gingivalis ◽  
Pathway Analysis ◽  
In Silico ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Medical Science ◽  
Bone Destruction ◽  
Therapeutic Drug ◽  
Potential Drug ◽  
Narrow Spectrum

Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear. Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrugresistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens. Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis. Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets. Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection. Bangladesh Journal of Medical Science Vol.20(4) 2021 p.887-896

Receptors, ion channels, and transporters as drug targets

2018 ◽  
pp. 149-189
Author(s):  
Norma Dunlap ◽  
Donna M. Huryn
Keyword(s):  
Ion Channels ◽  
Drug Targets

scholarly journals Accelerating Drug Discovery by Early Protein Drug Target Prediction Based on a Multi-Fingerprint Similarity Search †

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2233 ◽  
Author(s):  
Michele Montaruli ◽  
Domenico Alberga ◽  
Fulvio Ciriaco ◽  
Daniela Trisciuzzi ◽  
Anna Rita Tondo ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Similarity Search ◽  
Drug Targets ◽  
Search Algorithm ◽  
Confidence Score ◽  
Database Management System ◽  
Therapeutic Drug ◽  
Protein Drug ◽  
Early Protein

In this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which included more than half a million high-quality small molecules extracted from the latest release of ChEMBL (version 24.1, at the time of writing). Provided with a high biological assay confidence score, these selected compounds explored up to 2822 protein drug targets. To improve the data accuracy, samples marked as prodrugs or with equivocal biological annotations were not considered. Notably, MuSSel performances were overall improved by using an object-relational database management system based on PostgreSQL. In order to challenge the real effectiveness of MuSSel in predicting relevant therapeutic drug targets, we analyzed a pool of 36 external bioactive compounds published in the Journal of Medicinal Chemistry from October to December 2018. This study demonstrates that the use of highly curated chemical and biological experimental data on one side, and a powerful multi-fingerprint search algorithm on the other, can be of the utmost importance in addressing the fate of newly conceived small molecules, by strongly reducing the attrition of early phases of drug discovery programs.

Neuropeptide Y and its receptors as potential therapeutic drug targets

2002 ◽  
Vol 326 (1-2) ◽  
pp. 3-25 ◽  
Author(s):  
Antonio P Silva ◽  
Claudia Cavadas ◽  
Eric Grouzmann
Keyword(s):  
Neuropeptide Y ◽  
Drug Targets ◽  
Therapeutic Drug

Perivascular aquaporins: Potential postischemic therapeutic drug targets?*

2008 ◽  
Vol 36 (9) ◽  
pp. 2701-2702 ◽  
Author(s):  
Douglas D. Fraser ◽  
R David Andrew
Keyword(s):  
Drug Targets ◽  
Therapeutic Drug

scholarly journals Ageing impairs the airway epithelium defence response to SARS-CoV-2

2021 ◽  
Author(s):  
Alexander Capraro ◽  
Sharon L Wong ◽  
Anurag Adhikari ◽  
Katelin M Allan ◽  
Hardip R Patel ◽  
...  
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Viral Replication ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Defence Response ◽  
Nasal Epithelium ◽  
Therapeutic Drug ◽  
Healthy Children ◽  
Age Related

AbstractAge-dependent differences in the clinical response to SARS-CoV-2 infection is well-documented1–3 however the underlying molecular mechanisms involved are poorly understood. We infected fully differentiated human nasal epithelium cultures derived from healthy children (1-12 years old), young adults (26-34 years old) and older adults (56-62 years old) with SARS-COV-2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host defence response. We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic drug targets. Viral load was lowest in infected older adult cultures despite the highest expression of SARS-CoV-2 entry and detection factors. We showed this was likely due to lower expression of hijacked host machinery essential for viral replication. Unlike the nasal epithelium of young adults and children, global host response and induction of the interferon signalling was profoundly impaired in older adults, which preferentially expressed proinflammatory cytokines mirroring the “cytokine storm” seen in severe COVID-194,5. In silico screening of our virus-host-drug network identified drug classes with higher efficacy in older adults. Collectively, our data suggests that cellular alterations that occur during ageing impact the ability for the host nasal epithelium to respond to SARS-CoV-2 infection which could guide future therapeutic strategies.

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