Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites

2018 ◽  
Vol 25 (23) ◽  
pp. 2637-2660 ◽  
Author(s):  
Francesco Miceli ◽  
Maria V. Soldovieri ◽  
Paolo Ambrosino ◽  
Laura Manocchio ◽  
Ilaria Mosca ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Scientific Literature ◽  
New Drugs ◽  
Current Status ◽  
Functional Heterogeneity ◽  
Molecular Scaffolds ◽  
Kv7 Channels ◽  
Receptor Sites ◽  
Pharmacological Targets ◽  
Pharmacological Potential

Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for the development of new drugs for neuronal, cardiovascular and metabolic diseases. <p> Objective: In the present manuscript, we focus on describing the pharmacological relevance and potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. <p> Methods: The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. <p> Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. <p> Conclusion: In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases.

Upcoming Drifts In Bio-Similars

2020 ◽  
Vol 15 ◽  
Author(s):  
Geeta Aggarwal ◽  
Manju Nagpal ◽  
Ameya Sharma ◽  
Vivek Puri ◽  
Gitika Arora Dhingra
Keyword(s):  
Metabolic Diseases ◽  
Market Competition ◽  
Current Status ◽  
Medicinal Products ◽  
The Past ◽  
Biologic Activity ◽  
Emerging Trends ◽  
Regulatory Guidelines ◽  
Food Drug Administration ◽  
Insight Into

Background: Biopharmaceuticals such as Biologic medicinal products have been in clinical use over the past three decades and have benefited towards the therapy of degenerative and critical metabolic diseases. It is forecasted that market of biologics will be going to increase at a rate of 20% per year, and by 2025, more than ˃ 50% of new drug approvals may be biological products. The increasing utilization of the biologics necessitates for cost control, especially for innovators products that have enjoyed a lengthy period of exclusive use. As the first wave of biopharmaceuticals is expired or set to expire, it has led to various opportunities for the expansion of bio-similars i.e. copied versions of original biologics with same biologic activity. Development of biosimilars is expected to promote market competition, meet worldwide demand, sustain the healthcare systems and maintain the incentives for innovation. Methods: Appraisal of published articles from peer reviewed journals, PubMed literature, latest news and guidelines from European Medicine Agency, US Food Drug Administration (FDA) and India are used to identify data for review. Results: Main insight into the quality requirements concerning biologics, current status of regulation of biosimilars and upcoming challenges lying ahead for the upgrading of marketing authorization of bio-similars has been incorporated. Compiled literature on therapeutic status, regulatory guidelines and the emerging trends and opportunities of biosimilars has been thoroughly stated. Conclusion: Updates on biosimilars will support to investigate the possible impact of bio-similars on healthcare market.

scholarly journals Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 48
Author(s):  
Patricia Mondelo-Macía ◽  
Jorge García-González ◽  
Luis León-Mateos ◽  
Adrián Castillo-García ◽  
Rafael López-López ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
New Drugs ◽  
Current Status ◽  
Small Cell Lung ◽  
Tumor Biopsy ◽  
Future Utility

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

scholarly journals A Comprehensive Review of the Ethnotraditional Uses and Biological and Pharmacological Potential of the Genus Mimosa

2021 ◽  
Vol 22 (14) ◽  
pp. 7463
Author(s):  
Ismat Majeed ◽  
Komal Rizwan ◽  
Ambreen Ashar ◽  
Tahir Rasheed ◽  
Ryszard Amarowicz ◽  
...  
Keyword(s):  
Web Of Science ◽  
Scientific Literature ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Folk Medicine ◽  
Nutritional Values ◽  
Biological Potential ◽  
The World ◽  
The Future ◽  
Pharmacological Potential

The Mimosa genus belongs to the Fabaceae family of legumes and consists of about 400 species distributed all over the world. The growth forms of plants belonging to the Mimosa genus range from herbs to trees. Several species of this genus play important roles in folk medicine. In this review, we aimed to present the current knowledge of the ethnogeographical distribution, ethnotraditional uses, nutritional values, pharmaceutical potential, and toxicity of the genus Mimosa to facilitate the exploitation of its therapeutic potential for the treatment of human ailments. The present paper consists of a systematic overview of the scientific literature relating to the genus Mimosa published between 1931 and 2020, which was achieved by consulting various databases (Science Direct, Francis and Taylor, Scopus, Google Scholar, PubMed, SciELO, Web of Science, SciFinder, Wiley, Springer, Google, The Plant Database). More than 160 research articles were included in this review regarding the Mimosa genus. Mimosa species are nutritionally very important and several species are used as feed for different varieties of chickens. Studies regarding their biological potential have shown that species of the Mimosa genus have promising pharmacological properties, including antimicrobial, antioxidant, anticancer, antidiabetic, wound-healing, hypolipidemic, anti-inflammatory, hepatoprotective, antinociceptive, antiepileptic, neuropharmacological, toxicological, antiallergic, antihyperurisemic, larvicidal, antiparasitic, molluscicidal, antimutagenic, genotoxic, teratogenic, antispasmolytic, antiviral, and antivenom activities. The findings regarding the genus Mimosa suggest that this genus could be the future of the medicinal industry for the treatment of various diseases, although in the future more research should be carried out to explore its ethnopharmacological, toxicological, and nutritional attributes.

scholarly journals Current status of ticks and tick-host relationship in domestic and wild animals from Pantanal wetlands in the state of Mato Grosso do Sul, Brazil

2017 ◽  
Vol 107 (suppl) ◽  
Author(s):  
Paulo Henrique Duarte Cançado ◽  
João Luiz Horácio Faccini ◽  
Guilherme de Miranda Mourão ◽  
Eliane Mattos Piranda ◽  
Valéria Castilho Onofrio ◽  
...  
Keyword(s):  
Scientific Literature ◽  
Domestic Animals ◽  
Boophilus Microplus ◽  
Current Status ◽  
Good Representation ◽  
Hard Tick ◽  
Study Region ◽  
Mato Grosso ◽  
Mato Grosso Do Sul ◽  
Amblyomma Tigrinum

ABSTRACT This is a commented list of tick’s species collected on various wild and domestic animals, including the reports on scientific literature for the studied region. Most of animals were small or medium mammals. Carnivores were the main taxa group examined. Although, the pampas deer ( Ozotocerus bezoarticus) and giant anteater ( Mymercophaga tridactyla) also has a good representation on study. Among domestic animals, dogs, horses and cattle were examined. Summing up, 18 tick species were listed for the region. Sixteen were hard ticks (Ixodidae) and two soft ticks (Argasidae). Amblyomma sculptum was the most common and abundant hard tick. Ornithodoros rostratus (Argasidae) was very abundant, being the more important Argasidae tick on the study region. The following species were colleted or reported on scientific literature: Argas miniatus Koch, 1844; Ornithodoros rostratus Aragão, 1911; Dermacentor nitens Newmann, 1897; Rhipicephalus ( Boophilus) microplus Canestrini, 1887; Amblyomma tigrinum Koch, 1844; A. dissimile Koch, 1844; A. ovale Koch, 1844; A. pauvum Aragão, 1908; A. sculptum Berlese, 1888; A. calcaratum Neumann, 1899; A. coelebs Neumann, 1899; A. dubittatum Newmann, 1899; A. scalpturatum Newmann, 1906; A. naponense Packard, 1869; A. nodosum Newmann, 1899; A. pseudoconcolor Aragão, 1908; A. rotundatum Koch, 1844; A. triste Koch, 1844.

scholarly journals Empowering Melatonin Therapeutics with Drosophila Models

Diseases ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 67
Author(s):  
Cassandra Millet-Boureima ◽  
Caroline C. Ennis ◽  
Jurnee Jamison ◽  
Shana McSweeney ◽  
Anna Park ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Model Organism ◽  
New Drugs ◽  
Renal Diseases ◽  
Disease Pathogenesis ◽  
Multiple Functions ◽  
Functional Conservation ◽  
Oxidative Response ◽  
Pharmacological Potential ◽  
Drosophila Models

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.

scholarly journals Recent applications of quantitative analytical FTIR spectroscopy in pharmaceutical, biomedical, and clinical fields: A brief review

2022 ◽  
Vol 41 (1) ◽  
pp. 21-33
Author(s):  
Khairi Mustafa Fahelelbom ◽  
Abdullah Saleh ◽  
Moawia M. A. Al-Tabakha ◽  
Akram A. Ashames
Keyword(s):  
High Performance Liquid Chromatography ◽  
Fourier Transform ◽  
Ftir Spectroscopy ◽  
High Performance ◽  
Scientific Literature ◽  
Current Status ◽  
Full Potential ◽  
Biomedical Sciences ◽  
The Subject ◽  
Shed Light

Abstract Qualitative Fourier transform infrared (FTIR) spectroscopy has long been established and implemented in a wide variety of fields including pharmaceutical, biomedical, and clinical fields. While the quantitative applications are yet to reach their full potential, this technique is flourishing. It is tempting to shed light on modern engaging and the applicability of analytical quantitative FTIR spectroscopy in the aforementioned fields. More importantly, the credibility, validity, and generality of the application will be thoroughly demonstrated by reviewing the latest published work in the scientific literature. Utilizing FTIR spectroscopy in a quantitative approach in pharmaceutical, biomedical, and interdisciplinary fields has many undeniable advantages over traditional procedures. An insightful account will be undertaken in this regard. The technique will be introduced as an appealing alternative to common methods such as high performance liquid chromatography. It is anticipated that the review will offer researchers an update of the current status and prospect on the subject among the pharmacy and biomedical sciences both in academic and industrial fields.

scholarly journals LIPID METABOLISM DISEASES BY EXAMPLE GM2 GANGLIOZIDOSIS AND PREDISPOSITION TO THEM OF CERTAIN ETHNIC GROUPS OF PEOPLE

2020 ◽  
Vol 3 (2(71)) ◽  
pp. 34-36
Author(s):  
Z.V. Zyukina ◽  
T.A. Lobaeva
Keyword(s):  
Ethnic Groups ◽  
Metabolic Diseases ◽  
Scientific Literature ◽  
Research Result ◽  
The United States ◽  
Eastern European ◽  
Gm2 Gangliosidosis ◽  
Ashkenazi Jews ◽  
Hereditary Metabolic Diseases ◽  
Analytical Review

The relevance of the study is due to the fact that the scientific literature does not have sufficient data on the predisposition of certain ethnic groups of people to metabolic diseases on the example of GM2 gangliosidosis, so the purpose of the work is to clarify and analyze this predisposition of some ethnic groups of people to Tey — Sachs disease (GM2 gangliosidosis, amaurotic idiocy). The research materials and methods are a scientific and analytical review of modern publications on this topic. Research result: a review of the scientific literature has shown that the Jewish population of Eastern European origin (Ashkenazi Jews) has a higher incidence of TaySachs disease and other lipid accumulation diseases. Conclusions: the frequency of hereditary metabolic diseases ranges from 1: 2000 newborns to 1:1000000, and many of these diseases are characterized by differences in the frequency of occurrence in different ethnic groups and populations. In relation to GM2 gangliosidosis, it is shown that 1 in 27-30 Ashkenazi Jews in the United States is a recessive carrier of this disease. BTS affects 1 in 3,600 newborn Jews. One in 20 Jews have a hereditary predisposition to the disease.

scholarly journals Computational Tools in the Discovery of FABP4 Ligands: A Statistical and Molecular Modeling Approach

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 624 ◽  
Author(s):  
Giuseppe Floresta ◽  
Davide Gentile ◽  
Giancarlo Perrini ◽  
Vincenzo Patamia ◽  
Antonio Rescifina
Keyword(s):  
Fatty Acid Binding Protein ◽  
Metabolic Diseases ◽  
New Drugs ◽  
Computational Tools ◽  
Computer Aided Drug Design ◽  
Fatty Acid Binding ◽  
Property Prediction ◽  
Beneficial Effects ◽  
Acid Binding Protein

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered, but, unfortunately, none have reached the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches have been used for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. We retrieved 14,492 compounds from this database and filtered through them with a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 97–331 nM. ADMET property prediction was performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives. From these analyses, three molecules that are excellent candidates for becoming new drugs were found.

scholarly journals Drug Discovery against Acanthamoeba Infections: Present Knowledge and Unmet Needs

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 405 ◽  
Author(s):  
Hany M. Elsheikha ◽  
Ruqaiyyah Siddiqui ◽  
Naveed Ahmed Khan
Keyword(s):  
Recent Progress ◽  
Unmet Needs ◽  
Drug Repurposing ◽  
Present Knowledge ◽  
Current Status ◽  
Therapeutic Landscape ◽  
Pharmacological Targets ◽  
Health Complications ◽  
Interfering Rna ◽  
Made In

Although major strides have been made in developing and testing various anti-acanthamoebic drugs, recurrent infections, inadequate treatment outcomes, health complications, and side effects associated with the use of currently available drugs necessitate the development of more effective and safe therapeutic regimens. For any new anti-acanthamoebic drugs to be more effective, they must have either superior potency and safety or at least comparable potency and an improved safety profile compared to the existing drugs. The development of the so-called ‘next-generation’ anti-acanthamoebic agents to address this challenge is an active area of research. Here, we review the current status of anti-acanthamoebic drugs and discuss recent progress in identifying novel pharmacological targets and new approaches, such as drug repurposing, development of small interfering RNA (siRNA)-based therapies and testing natural products and their derivatives. Some of the discussed approaches have the potential to change the therapeutic landscape of Acanthamoeba infections.

scholarly journals Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1216
Author(s):  
Seigo Kimura ◽  
Hideyoshi Harashima
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Neurological Disorders ◽  
Viral Vectors ◽  
New Drugs ◽  
Brain Targeting ◽  
Current Status ◽  
Great Promise ◽  
Targeted Gene Delivery ◽  
The Central Nervous System

The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a significant impact on society, both globally and socially. Gene therapy has great promise for the treatment of neurological disorders, but only a few gene therapy drugs are currently available. Delivery to the brain is the biggest hurdle in developing new drugs for the central nervous system (CNS) diseases and this is especially true in the case of gene delivery. Nanotechnologies such as viral and non-viral vectors allow efficient brain-targeted gene delivery systems to be created. The purpose of this review is to provide a comprehensive review of the current status of the development of successful drug delivery to the CNS for the treatment of CNS-related disorders especially by gene therapy. We mainly address three aspects of this situation: (1) blood-brain barrier (BBB) functions; (2) adeno-associated viral (AAV) vectors, currently the most advanced gene delivery vector; (3) non-viral brain targeting by non-invasive methods.

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