Expert Opinion on Therapeutic Targets

BACKGROUND: Pre-existing hypertensive pathologies are linked to worsened outcomes in patients infected with severe-acute respiratory syndrome (SARS-CoV-2). Sartans, a family of anti-hypertensive angiotensin receptor blockers (ARBs), reduce morbidity and mortality in coronavirus 2019 patients by aeffecting angiotensin-converting enzyme-2 (ACE2). The purpose of this study was to determine the anti-SARS-CoV-2viral and antihypertensive abilities of nirmatrelvir, and commercially available (e...

INTRODUCTION: Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide, despite widespread use of statins. There is a need to develop additional therapeutic strategies that will complement statins in order to achieve more effective reductions in cardiovascular risk. AREAS COVERED: This review provides a comprehensive summary of current areas of therapeutic development targeting both lipid and inflammatory factors implicated in the pathogenesis of atherosclerosis...

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field...

No abstract text is available yet for this article.

INTRODUCTION: Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems. AREAS COVERED: We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity...

INTRODUCTION: Collagen triple helix repeat containing 1 (CTHRC1) is a protein that has been implicated in pro-migratory pathways, arterial tissue-repair processes, and inhibition of collagen deposition via the regulation of multiple signaling cascades. Studies have also demonstrated an upregulation of CTHRC1 in multiple cancers where it has been linked to enhanced proliferation, invasion, and metastasis. However, the understanding of the exact role and mechanisms of CTHRC1 in cancer is far from complete...

INTRODUCTION: Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T cells, B cells, dendritic cells, and other immune cells. Loss of HPK1 kinase activity results in exacerbated cytokine secretion, enhanced T cell signaling, improved viral clearance, and thus increased restraint of tumor growth. These findings highlight HPK1 as a promising target for immuno-oncology treatments, culminating in the advancement of candidate compounds targeting HPK1 to clinical trials by several biotech enterprises...

BACKGROUND: The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. Natural compounds that can complement combination radiation therapy need to be identified. Arenobufagin is commonly used for heart diseases and liver cancer, but its effectiveness in NPC is unclear. STUDY DESIGN AND METHODS: The effect of arenobufagin-induced apoptosis was measured by a cell viability assay, tumorigenic assay, fluorescence assay, and Western blot assay through NPC-039 and NPC-BM cell lines...

INTRODUCTION: Multiple interventions have demonstrated an increase in mouse lifespan. However, non-standardized controls, sex or strain-specific factors, and insufficient focus on targets, hinder the translation of these findings into clinical applications. AREAS COVERED: We examined the effects of genetic and drug-based interventions on mice from databases DrugAge, GenAge, the Mouse Phenome Database, and publications from PubMed that led to a lifespan extension of more than 10%, identifying specific molecular targets that were manipulated to achieve the maximum lifespan in mice...

INTRODUCTION: Phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been implicated in many types of cancers. The PRL family of phosphatases consists of three members, PRL1, PRL2, and PRL3. PRLs have been shown to harbor oncogenic potentials and are highly expressed in a variety of cancers. Given their roles in cancer progression and metastasis, PRLs are potential targets for anticancer therapies. However, additional studies are needed to be performed to fully understand the roles of PRLs in blood cancers...

INTRODUCTION: The phosphatidylinositol-3-kinase (PI3K) pathway is a crucial intracellular signaling pathway involved in cell growth, proliferation, survival, and metabolism, which is aberrant in almos<u>t</u> all types of cancer. Extensive research is dedicated to elucidating the mechanisms of action and developing PI3K inhibitors. However, only a small portion of the research has been successfully translated into clinical applications. AREAS COVERED: In this review, we present an overview of the pivotal role that the PI3K pathway plays in tumor development...

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease induced by viral infection or vaccination. With the increased incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the incidence of AA has also increased. Recently the incidence was found to be 7.8% from a previously reported rate of 2.1%. The physical and psychological damage caused by AA could seriously affect patients' lives, while AA is a challenging dermatological disease owing to its complex pathogenesis...

No abstract text is available yet for this article.

OBJECTIVES: Salmonella Typhi biofilm condition is showing as a major public health problem due to the developmentof antibiotic resistance and less available druggable target proteins.Therefore, we aimed to identify some more druggable targets of S . Typhi biofilm using computational drilling at the genome/proteome level so that thetarget shortage problem could be overcome and more antibiofilm agents could bedesigned in the future against the disease. METHODS: We performed protein-protein dockingand interaction analysis between the homological identified target proteins of S...

INTRODUCTION: Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include > 20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed. AREAS COVERED: Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy...

INTRODUCTION: Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction. AREAS COVERED: In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2×3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide - dependent pathways, and MaxiK±channel - gene therapy. EXPERT OPINION: TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists...

BACKGROUND: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. RESEARCH DESIGN AND METHODS: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i...

BACKGROUND: Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explored how galanin receptor 2 (GALR2) and Neuropeptide Y1 Receptor (NPYY1R) agonists, working together, can boost brain cell growth and increase antidepressant-like effects in rats. This suggests new ways to treat Major Depressive Disorder (MDD). RESEARCH DESIGN AND METHODS: In a controlled laboratory setting, adult naive Sprague-Dawley rats were administered directly into the brain's ventricles, a method known as intracerebroventricular (ICV) administration, with GALR2 agonist (M1145), NPYY1R agonist, both, or in combination with a GALR2 antagonist (M871)...

INTRODUCTION: Microtubules play a vital role in cancer therapeutics. They are implicated in tumorigenesis, thus inhibiting tubulin polymerization in cancer cells, and have now become a significant target for anticancer drug development. A plethora of drug molecules has been crafted to influence microtubule dynamics and presently, numerous tubulin inhibitors are being investigated. This review discusses the recently developed inhibitors including natural products, and also examines the preclinical and clinical data of some potential molecules...

INTRODUCTION: The pathways like Wingless-related integration (Wnt/β-catenin) and PI3K play an important role in colorectal cancer (CRC) development, however, their roles are distinct in the process of oncogenesis. Despite their differences, these pathways interact through feedback mechanisms and regulate the common effectors both in the upstream as well as the downstream processes in normal and pathological conditions. Their ability to reciprocally control each other is a primary resistance mechanism for the selective inhibitors in CRC...