P2X3 Receptor Ligands: Structural Features and Potential Therapeutic Applications.
Ontology highlight
ABSTRACT:
SUBMITTER: Spinaci A
PROVIDER: S-EPMC8076795 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure-activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.
| S-EPMC9611956 | biostudies-literature
Project description:Snake venom metalloproteinases (SVMPs) are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogen)olytic activity. Their main biological substrate is fibrin(ogen), whose A?-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a) they are insensitive to plasma serine proteinase inhibitors; (b) they have the potential to avoid bleeding risk; (c) mechanistically, they are inactivated/cleared by ?2-macroglobulin that limits their range of action in circulation; and (d) few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure-function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.
| S-EPMC5744112 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) have shown their therapeutic potency for treatment of cardiovascular diseases owing to their low immunogenicity, ease of isolation and expansion, and multipotency. As multipotent progenitors, MSCs have revealed their ability to differentiate into various cell types and could promote endogenous angiogenesis via microenvironmental modulation. Studies on cardiovascular diseases have demonstrated that transplanted MSCs could engraft at the injured sites and differentiate into cardiomyocytes and endothelial cells as well. Accordingly, several clinical trials using MSCs have been performed and revealed that MSCs may improve relevant clinical parameters in patients with vascular diseases. To fully comprehend the characteristics of MSCs, understanding their intrinsic property and associated modulations in tuning their behaviors as well as functions is indispensable for future clinical translation of MSC therapy. This review will focus on recent progresses on endothelial differentiation and potential clinical application of MSCs, with emphasis on therapeutic angiogenesis for treatment of cardiovascular diseases.
| S-EPMC4736816 | biostudies-other
Project description:Macrocyclic peptides are an emerging class of bioactive compounds for therapeutic use. In part, this is because they are capable of high potency and excellent target affinity and selectivity. Over the last decade, several biochemical techniques have been developed for the identification of bioactive macrocyclic peptides, allowing for the rapid isolation of high affinity ligands to a target of interest. A common feature of these techniques is a general reliance on thioether formation to effect macrocyclization. Increasingly, the compounds identified using these approaches have been subjected to x-ray crystallographic analysis bound to their respective targets, providing detailed structural information about their conformation and mechanism of target binding. The present review provides an overview of the target bound thioether-closed macrocyclic peptide structures that have been obtained to date.
| S-EPMC6316662 | biostudies-literature
Project description:To identify and highlight the feasibility, challenges, and advantages of providing a cross-domain pipeline that can link relevant biodiversity information for phyto-therapeutic assessment.A public repository of clinical trials information (ClinicalTrials.gov) was explored to determine the state of plant-based interventions under investigation.The results showed that ? 15% of drug interventions in ClinicalTrials.gov were potentially plant related, with about 60% of them clustered within 10 taxonomic families. Further analysis of these plant-based interventions identified ? 3.7% of associated plant species as endangered as determined from the International Union for the Conservation of Nature Red List.The diversity of the plant kingdom has provided human civilization with life-sustaining food and medicine for centuries. There has been renewed interest in the investigation of botanicals as sources of new drugs, building on traditional knowledge about plant-based medicines. However, data about the plant-based biodiversity potential for therapeutics (eg, based on genetic or chemical information) are generally scattered across a range of sources and isolated from contemporary pharmacological resources. This study explored the potential to bridge biodiversity and biomedical knowledge sources.The findings from this feasibility study suggest that there is an opportunity for developing plant-based drugs and further highlight taxonomic relationships between plants that may be rich sources for bioprospecting.
| S-EPMC3721164 | biostudies-literature
Project description:The discovery of a highly selective putative sigma-1 (σ1) receptor agonist, PRE-084, has revealed the numerous potential uses of this receptor subtype as a therapeutic target. While much work has been devoted to determining the role of σ1 receptors in normal and pathophysiological states in the nervous system, recent work suggests that σ1 receptors may be important for modulating functions of other tissues. These discoveries have provided novel insights into σ1 receptor structure, function, and importance in multiple intracellular signaling mechanisms. These discoveries were made possible by σ1 receptor-selective agonists such as PRE-084. The chemical properties and pharmacological actions of PRE-084 will be reviewed here, along with the expanding list of potential therapeutic applications for selective activation of σ1 receptors.
| S-EPMC7484451 | biostudies-literature
Project description: Not available
| S-EPMC8850518 | biostudies-literature
Project description:Estrogen receptors, comprised of ER? and ER? isoforms in mammals, act as ligandmodulated transcription factors and orchestrate a plethora of cellular functions from sexual development and reproduction to metabolic homeostasis. Herein, I revisit the structural basis of the binding of ER? to DNA and estradiol in light of the recent discoveries and emerging trends in the field of nuclear receptors. A particular emphasis of this review is on the chemical and structural diversity of an everincreasing repertoire of physiological, environmental and synthetic ligands of estrogen receptors that ultimately modulate their interactions with cognate DNA located within the promoters of estrogenresponsive genes. In particular, modulation of estrogen receptors by small molecule ligands represents an important therapeutic goal toward the treatment of a wide variety of human pathologies including breast cancer, cardiovascular disease, osteoporosis and obesity. Collectively, this article provides an overview of a wide array of small organic and inorganic molecules that can fine-tune the physiological function of estrogen receptors, thereby bearing a direct impact on human health and disease.
| S-EPMC4604006 | biostudies-literature
Project description:G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300,000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein-Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.
| S-EPMC4227801 | biostudies-literature
Project description:Pinocembrin is a natural flavonoid compound extracted from honey, propolis, ginger roots, wild marjoram, and other plants. In preclinical studies, it has shown anti-inflammatory and neuroprotective effects as well as the ability to reduce reactive oxygen species, protect the blood-brain barrier, modulate mitochondrial function, and regulate apoptosis. Considering these pharmaceutical characteristics, pinocembrin has potential as a drug to treat ischemic stroke and other clinical conditions. In this review, we summarize its pharmacologic characteristics and discuss its mechanisms of action and potential therapeutic applications.
| S-EPMC4561606 | biostudies-other