Current drug targets最新文献

Neuron loss is the main feature of neurodegenerative diseases. The two most prevalent neurodegenerative illnesses are Parkinson's and Alzheimer's diseases. While several medications are currently approved to treat neurodegenerative disorders, most of them only address the symptoms that are related to the disorders. Owing to their severity and complex multifactorial pathophysiology, the approved medications currently in clinical use have not demonstrated sufficient efficacy and have limited therapeutic options. Enhancing medicine quality can be achieved using highly efficient conjugate chemistry methods, necessitating ongoing discovery efforts on hybrid drugs in academia and industry. The present review illustrates hybrid compounds and the design strategies that helped to create them. Developing multi-target directed ligands (MTDLs) is a more advantageous and sensible strategy for treating long-term complex illnesses like neurodegenerative diseases. Compared to classic treatments, hybrid drugs can deliver combination therapies in a single multifunctional agent, making them more potent and specific. Three main objectives are being initiated by using hybridization techniques in drug design: (i) increasing selectivity, (ii) improving activity, and (iii) reducing toxicity. The development of hybrid medications may offer a valuable method for producing compounds that are less likely to develop resistance and more likely to be effective. Hybrid drugs hold great promise, but a few technical and regulatory obstacles must be overcome before they can be successfully used in clinical settings.

A range of heterocyclic compounds, including Isatin (oneH-indole-2, 3-dione) and its by-products, have been shown to represent potential unit blocks in the synthesis of potential medicinal agents. Numerous studies have been carried out on isatin, its synthesis, biological uses, and its chemical composition since when it was discovered. Functionally, these isatin-containing heterocycles have demonstrated antibacterial, antidiabetic, antiviral, antitubercular, and anticancer properties, among many others. In vitro and In vivo efficaciousness of several Isatin moieties has been assessed in recent years based on their antimicrobial qualities. Isatin has shown great promise as a flexible heterocycle in the realm of drug development in recent years. Many viruses have caused extensive epidemics during the last 50 years, which have had detrimental effects on social, economic, and health conditions. The current unprecedented SARS-CoV-2 epidemic necessitates intensive research into the development of potent antiviral medications. It has been shown that Isatin, a flexible heterocycle, has a great deal of potential for drug development. Appropriately functionalized Isatin compounds have shown noteworthy and extensive antiviral activities throughout the last fifty years. The goal of this study is to gather all known data on Isatin derivatives' antiviral activity, emphasizing their structure-activity correlations as well as research on mechanistic and molecular modelling. We think that the scientific community will find this review to be a useful tool in the development of more efficient and powerful antiviral treatments based on Isatin scaffolds.

Background: Epilepsy is a multifaceted neurological disorder marked by seizures that can present with a wide range of symptoms. Despite the prevalent use of anti-epileptic drugs, drug resistance and adverse effects present considerable obstacles. Despite advancements in anti-epileptic drugs (AEDs), approximately 20-30% of patients remain drug-resistant, highlighting the need for innovative therapeutic strategies.

Aim: This study aimed to explore advancements in epilepsy diagnosis and treatment utilizing modern technology and medicines.

Methods: The literature survey was carried out using Scopus, ScienceDirect, and Google Scholar. Data from the last 10 years were preferred to include in the study.

Result: Emerging technologies, such as artificial intelligence, gene therapy, and wearable gadgets, have transformed epilepsy care. EEG and MRI play essential roles in diagnosis, while AI aids in evaluating big datasets for more accurate seizure identification. Machine learning and artificial intelligence are increasingly integrated into diagnostic processes to enhance seizure detection and classification. Wearable technology improves patient self-monitoring and helps clinical research. Furthermore, gene treatments offer promise by treating the fundamental causes of seizure activity, while stem cell therapies give neuroprotective and regenerative advantages. Dietary interventions, including ketogenic diets, are being examined for their ability to modify neurochemical pathways implicated in epilepsy.

Conclusion: Recent technological and therapeutic developments provide major benefits in epilepsy assessment and treatment, with AI and wearable devices enhancing seizure detection and patient monitoring. Nonetheless, additional study is essential to ensure greater clinical application and efficacy. Future perspectives include the potential of optogenetics and advanced signal processing techniques to revolutionize treatment paradigms, emphasizing the importance of personalized medicine in epilepsy care. Overall, a comprehensive understanding of the multifaceted nature of epilepsy is essential for developing effective interventions and improving patient outcomes.

Introduction: Breast cancer incidence and mortality have continued to rise over the past few decades. Despite advancements made in clinical research, the most imperative feature of breast cancer management is the diagnosis at the earliest stages. The current focus of the study is to identify and quantify differentially expressed oxidative stress-related proteins as putative early- stage markers for breast cancer.

Methods: Normal and cancerous breast tissue samples (n = 40) were collected after approval from the institutional bioethics committee (IBC) and with patient's consent. A label-free proteomic approach was used to quantify oxidative stress-related proteins. Gene expression of GSTP1, PRDX2, HSP90, NFE2L2, and miR-365a was quantified using RT-qPCR in all samples. Protein expression of PRDX2 and GSTP1 was further analyzed using immunohistochemistry.

Results: The protein and gene expression of PRDX2, GSTP1, and HSP90 were significantly upregulated (p < 0.05) in cancerous samples as compared to normal. However, gene and protein expression of the transcription factor NFE2L2 was significantly downregulated (p < 0.05) in diseased samples. OncomiR-365a was also significantly upregulated (p < 0.05) in cancerous samples. Immunohistochemical analysis also confirmed the upregulated expression of GSTP1 and PRDX2 in cancer tissues.

Discussion: Our study provides insight into the significant role of GSTP1, PRDX2, and NFE2L2 in the pathophysiology of the disease as early-stage breast cancer markers. It is suggested that altered expression of these key proteins could play a protective role in reducing the damage.

Conclusion: It can be concluded that GSTP1, PRDX2, and NFE2L2 may serve as predictive early- stage markers for diagnosis and potential therapeutic targets for breast cancer.

Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestingly, the amylin receptor is the heterodimer of the calcitonin receptor (which is the receptor for the peptide hormone calcitonin) and an accessory protein called receptor activity-modifying protein. Amylin receptor activation has emerged as a promising drug target for the treatment of diabetes and obesity. Recent pharmaceutical efforts with amylin receptor activators have focused on developing drugs for the treatment of obesity. Multiple amylin analogs have been tested in pre-clinical settings, and some are currently being tested in clinical trials. For this review, recent research publications and available information regarding drug development targeting amylin receptors were collected. This review summarizes the amylin receptor activators currently being tested in clinical trials for the treatment of obesity. In addition, recent research achievements were demonstrated, such as the introduction of mutations that enhanced receptor affinity/potency and the development of a method for measuring selective amylin receptor activation. Potential issues along with peptide drug development were described, including lipidation to achieve a long-acting property. The combination of an amylin analog and other anti-obesity peptide drugs has demonstrated higher clinical efficacy in reducing body weight than monotherapy. The combination therapy is likely to be the first drug therapy where an amylin analog is used for obesity treatment. In addition, amylin receptor activators may have an adverse effect profile more favorable than that of GLP-1 receptor activators, which could be a potential benefit of amylin receptor activators.

Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking inflammation to lung cancer progression, with both pro-tumor and anti-tumor effects. This perspective delves into the complex functions of TLR proteins in lung cancers, elucidating their involvement in tumor growth, angiogenesis, and metastasis. In addition, we highlight the therapeutic potentials of TLR agonists and antagonists, emphasizing their interplay with immune checkpoint inhibitors like PD-1/PD-L1 blockers to overcome immunosuppressive barriers. Nevertheless, the paradoxical effects of TLR activation, balancing immune stimulation and suppression, demand precise targeting strategies. Collectively, our study synthesizes the current understanding of TLR signaling pathways in lung cancers, offering insights into their potential for advancing lung cancer therapies.

This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.

The family of proteins known as Bromodomain and Extra-Terminal (BET) proteins has become a key participant in the control of gene expression, having a significant impact on numerous physiological and pathological mechanisms. This review offers a thorough investigation of the BET protein family, clarifying its various roles in essential cellular processes and its connection to a variety of illnesses, from inflammatory disorders to cancer. The article explores the structural and functional features of BET proteins, emphasizing their special bromodomain modules that control chromatin dynamics by identifying acetylated histones. BET proteins' complex roles in the development of cardiovascular, neurodegenerative, and cancer diseases are carefully investigated, providing insight into possible treatment avenues. In addition, the review carefully examines the history and relevance of BET inhibitors, demonstrating their capacity to modify gene expression profiles and specifically target BET proteins. The encouraging outcomes of preclinical and clinical research highlight BET inhibitors' therapeutic potential across a range of disease contexts. The article summarizes the state of BET inhibitors today and makes predictions about the challenges and future directions of the field. This article provides insights into the changing field of BET protein-targeted interventions by discussing the potential of personalized medicine and combination therapies involving BET inhibitors. This thorough analysis combines many aspects of BET proteins, such as their physiological roles and their roles in pathophysiological conditions. As such, it is an invaluable tool for scientists and medical professionals who are trying to figure out how to treat patients by using this fascinating protein family.

The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.

Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.