Current drug targets最新文献

{"title":"GPR56, an Adhesion GPCR with Multiple Roles in Human Diseases, Current Status and Future Perspective.","authors":"Yan Fan, Xiao-Yan Yan, Wei Guan","doi":"10.2174/0113894501298344240507080149","DOIUrl":"10.2174/0113894501298344240507080149","url":null,"abstract":"<p><p>Human G protein-coupled receptor 56 (GPR56) belongs to a member of the adhesion G-protein coupled receptor (aGPCR) family and widely exists in the central nervous system and various types of tumor tissues. Recent studies have shown that abnormal expression or dysfunction of GPR56 is closely associated with many physiological and pathological processes, including brain development, neuropsychiatric disorders, cardiovascular diseases and cancer progression. In addition, GPR56 has been proven to enhance the susceptibility of some antipsychotics and anticarcinogens in response to the treatment of neuropsychological diseases and cancer. Although there have been some reports about the functions of GPR56, the underlying mechanisms implicated in these diseases have not been clarified thoroughly, especially in depression and epilepsy. Therefore, in this review, we described the molecular structure and signal transduction pathway of GPR56 and carried out a comprehensive summary of GPR56's function in the development of psychiatric disorders and cancer. Our review showed that GPR56 deficiency led to depressive-like behaviors and an increase in resistance to antipsychotic treatment. In contrast, the upregulation of GPR56 contributed to tumor cell proliferation and metastasis in malignant diseases such as glioblastoma, colorectal cancer, and ovarian cancer. Moreover, we elucidated specific signaling pathways downstream of GPR56 related to the pathogenesis of these diseases. In summary, our review provides compelling arguments for an attractive therapeutic target of GPR56 in improving the therapeutic efficiency for patients suffering from psychiatric disorders and cancer.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"558-573"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Understanding and Managing Alzheimer's Disease: From Pathophysiology to Innovative Therapeutic Strategies.","authors":"Sunny Rathee, Debasis Sen, Vishal Pandey, Sanjay K Jain","doi":"10.2174/0113894501320096240627071400","DOIUrl":"10.2174/0113894501320096240627071400","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by the presence of amyloid-β (Aβ) plaques and tau-containing neurofibrillary tangles, leading to cognitive and physical decline. Representing the majority of dementia cases, AD poses a significant burden on healthcare systems globally, with onset typically occurring after the age of 65. While most cases are sporadic, about 10% exhibit autosomal forms associated with specific gene mutations. Neurofibrillary tangles and Aβ plaques formed by misfolded tau proteins and Aβ peptides contribute to neuronal damage and cognitive impairment. Currently, approved drugs, such as acetylcholinesterase inhibitors and N-methyl D-aspartate receptor agonists, offer only partial symptomatic relief without altering disease progression. A promising development is using lecanemab, a humanized IgG1 monoclonal antibody, as an immune therapeutic approach. Lecanemab demonstrates selectivity for polymorphic Aβ variants and binds to large soluble Aβ aggregates, providing a potential avenue for targeted treatment. This shift in understanding the role of the adaptive immune response in AD pathogenesis opens new possibilities for therapeutic interventions aiming to address the disease's intricate mechanisms. This review aims to summarize recent advancements in understanding Alzheimer's disease pathophysiology and innovative therapeutic approaches, providing valuable insights for both researchers and clinicians.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"752-774"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Total Parenteral Nutrition (TPN) as a Vehicle for Drug Delivery.","authors":"Hossamaldeen Bakrey, Riya Shivgotra, Abdulkadir Abdu, Bindu Soni, Navid Reza Shahtaghia, Subheet Kumar Jain, Shubham Thakur","doi":"10.2174/0113894501284598240226102943","DOIUrl":"10.2174/0113894501284598240226102943","url":null,"abstract":"<p><p>Total Parenteral Nutrition (TPN) is a method of providing nutrients directly into the bloodstream for individuals who are unable to meet their nutritional needs through the normal digestive process or gastrointestinal system. It provides macronutrients and micronutrients in a single container, reducing handling and contamination risks and making it more cost-effective. TPN has the potential to be used as a drug delivery system, with applications in combination therapies, personalized medicine, and integrating advanced technologies. It can enhance drug dosage precision and provide nutritional assistance, potentially reducing hospitalization and improving patient outcomes. However, implementing new applications requires thorough testing and regulatory approval. TPN could be particularly useful in pediatric and geriatric care and could also contribute to global health by combating malnutrition in areas with limited medical resources. Healthcare professionals prepare a sterile solution tailored to each patient's nutritional needs, and administration involves a central venous catheter. However, the simultaneous administration of medications with PN admixtures can result in pharmacological incompatibility, which can impact the stability of the oil-in-water system. The European Society for Clinical Nutrition and Metabolism and the American Society for Parenteral and Enteral Nutrition recommendations advise against including non-nutrient drugs in PN admixtures due to safety concerns. This review focuses on the utilization of Total Parenteral Nutrition (TPN) as a method for delivering drugs. It discusses the benefits and difficulties associated with its commercial application and offers suggestions for future research endeavors.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"306-329"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Contemporary and Future Therapeutic Strategies for Scalp Psoriasis.","authors":"Bindu Soni, Riya Shivgotra, Karan Trehan, Aashveen Chhina, Muskaan Saini, Subheet Kumar Jain, Shubham Thakur","doi":"10.2174/0113894501292755240304063020","DOIUrl":"10.2174/0113894501292755240304063020","url":null,"abstract":"<p><p>Scalp psoriasis is a common manifestation of psoriasis that significantly impacts a patient's quality of life. About 80% of cases of psoriasis involve the scalp, making it the most frequently affected area of the body. The treatment of scalp psoriasis is particularly crucial because of its hard-to-treat nature and substantial adverse impacts on overall well-being. Along with the physical symptoms of discomfort and itching, psoriasis, especially when it affects the scalp, can cause severe psychological damage. Treating scalp psoriasis can be challenging due to its location and associated symptoms, such as scaling and pruritus, which is why various drugs have become widely used for refractory cases. Topical treatments like corticosteroids and vitamin D analogs manage scalp psoriasis by reducing inflammation and regulating skin cell growth. Tar-based shampoos, salicylic acid solutions, and moisturizers control scaling. Phototherapy with UVB light reduces inflammation. Severe cases may require systemic medications such as oral retinoids and immunosuppressants. While various therapies are accessible for scalp psoriasis, concerns arise due to their limited advantages and the absence of controlled studies assessing their effectiveness. Considering these challenges, there is a clear demand for innovative approaches to address this condition effectively. Recent advancements in topical therapies, phototherapy, systemic agents, and complementary therapies have shown promising results in managing scalp psoriasis. Also, the advent of biologics, specifically anti-IL-17 and anti-IL-23 drugs for scalp psoriasis, has seen significant improvements. The review highlights the lack of well-tolerated and effective treatments for scalp psoriasis and underscores the importance of further research in this area. The objective of this review is to clarify the different treatment options currently available or being investigated in clinical trials for managing scalp psoriasis.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"353-373"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiobesity Drug Discovery Research: <i>In vitro</i> Models for Shortening the Drug Discovery Pipeline.","authors":"Radheshyam, Priyanka Gauniya, Mona Semalty, Ajay Semalty","doi":"10.2174/0113894501289136240312060838","DOIUrl":"10.2174/0113894501289136240312060838","url":null,"abstract":"<p><p>Obesity is a growing global health problem, leading to various chronic diseases. Despite standard treatment options, the prevalence of obesity continues to rise, emphasizing the need for new drugs. <i>in vitro</i> methods of drug discovery research provide a time and cost-saving platform to identify new antiobesity drugs. The review covers various aspects of obesity and drug discovery research using <i>in vitro</i> models. Besides discussing causes, diagnosis, prevention, and treatment, the review focuses on the advantages and limitations of <i>in vitro</i> studies and exhaustively covers models based on enzymes and cell lines from different animal species and humans. In contrast to conventional in vivo animal investigations, <i>in vitro</i> preclinical tests using enzyme- and cell line-based assays provide several advantages in development of antiobesity drugs. These methods are quick, affordable, and provide high-throughput screening. They can also yield insightful information about drug-target interactions, modes of action, and toxicity profiles. By shedding light on the factors that lead to obesity, <i>in vitro</i> tests can also present a chance for personalized therapy. Technology will continue to evolve, leading to the creation of more precise and trustworthy <i>in vitro</i> assays, which will become more and more crucial in the search for novel antiobesity medications.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"388-403"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebentafusp as a Promising Drug for the Treatment of Uveal Melanoma.","authors":"Khalid Al Balushi, Abdulrahman Al Hadhrami, Hamdan Al Balushi, Abdullah Al Lawati, Srijit Das","doi":"10.2174/0113894501280380231214105255","DOIUrl":"10.2174/0113894501280380231214105255","url":null,"abstract":"<p><p>Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and commonly occurs in the Caucasian population. The malignancy involves the uvea of the eye, which includes the iris, ciliary body, and choroid. The etiology of UM is still not well understood, but age is a risk factor. Symptoms include blurred vision, redness of the eye, floaters, dark spots, a change in the size of the pupil, and loss of vision. The location, shape, and size of the tumor are important for therapeutic purposes. Treating metastasis is always a challenge in UM cases. In cases of lung metastasis, the survival rate decreases. Treatment includes surgery, laser therapy, immunotherapy, hormone therapy, and chemotherapy. Recently, in 2022, the United States Food and Drug Administration (FDA) approved the drug tebentafusp. Tebentafusp was developed to target the most common HLA complex in humans. The present review discusses the indications for the use of a new drug tebentafusp, its mechanism of action, dose, pharmacokinetics, results of clinical trials conducted, and adverse effects like cytokine release syndrome. Hence, tebentafusp is the first T cell receptor (TCR) therapeutic drug that could be considered for the treatment of UM.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"149-157"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact.","authors":"Debayan Sil, Shreastha Gautam, Shubhi Saxena, Sachin Joshi, Dinesh Kumar, Astha Mehta, Priya Jindal, Subhi Sharma, Prachi Pandey, Diksha, Amandeep Singh","doi":"10.2174/0113894501296586240430061915","DOIUrl":"10.2174/0113894501296586240430061915","url":null,"abstract":"<p><p>The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 (\"Arcturus\"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as \"Eris,\" has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a \"variant of interest\" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"517-525"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing Skin Cancer Treatment: The Rise of PD-1/PDL-1 and CTLA-4 as Key Therapeutic Targets.","authors":"Neha Sharma, Rupa Mazumder, Pallavi Rai","doi":"10.2174/0113894501320281240822052657","DOIUrl":"10.2174/0113894501320281240822052657","url":null,"abstract":"<p><p>Skin cancer is a significant health concern, affecting millions of individuals globally on an annual basis. According to data from the World Health Organization, it stands as the most prevalent form of cancer within the white population. Current treatments for skin cancer typically involve a combination of chemotherapy, radiation therapy, and surgery. However, these methods often come with drawbacks, such as side effects and potential scarring. Therefore, there is a growing need for alternative treatments that can offer effective results with fewer adverse effects, driving ongoing research in skin cancer therapy. The advancement of immune checkpoint inhibitors has been facilitated by a more profound comprehension of the interplay between tumors and the immune system, along with the regulatory mechanisms governing T-cells. As cancer treatment continues to evolve, immunotherapy is emerging as a powerful strategy, leading to a growing interest in the role of immunological checkpoints in skin cancer. Various types of immune checkpoints and their expression, including PD-1, PDL-1, CTLA-4, lymphocyte activation gene 3, and B7-H3, along with their blockers and monoclonal antibodies, have been established for various cancers. PD-1, PDL-1, and CTLA-4 are crucial immune system regulators, acting as brakes to prevent T-- cell overactivation and potential autoimmunity. However, tumors can exploit these checkpoints to evade immune detection. Inhibiting these immune checkpoints can enhance the body's ability to recognize and attack cancer cells. This review focuses on the characteristics of PD-1, PDL-1, and CTLA-4 immune checkpoints, their mechanism of action, and their role in skin cancer. Additionally, it summarizes the ongoing clinical trials sponsored or conducted by various pharmaceutical companies and provides insights into the latest patent data.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"1012-1026"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Barriers: Current Advances and Future Directions in Mpox Therapy.","authors":"Bhumi M Shah, Palmi Modi","doi":"10.2174/0113894501281263231218070841","DOIUrl":"10.2174/0113894501281263231218070841","url":null,"abstract":"<p><strong>Background: </strong>Mpox, a newly discovered zoonotic infection, can be transmitted from animal to human and between humans. Serological and genomic studies are used to identify the virus.</p><p><strong>Objective: </strong>Currently, there are no proven effective treatments for Mpox. Also, the safety and efficacy of intravenous vaccinia immune globulin, oral Tecovirimat (an inhibitor of intracellular viral release), and oral Brincidofovir (a DNA polymerase inhibitor) against the Mpox virus are uncertain, highlighting the need for more effective and safe treatments. As a result, drug repurposing has emerged as a promising strategy to identify previously licensed drugs that can be repurposed to treat Mpox.</p><p><strong>Results: </strong>Various approaches have been employed to identify previously approved drugs that can target specific Mpox virus proteins, including thymidylate kinase, D9 decapping enzyme, E8 protein, Topoisomerase1, p37, envelope proteins (D13, A26, and H3), F13 protein, virus's main cysteine proteases, and DNA polymerase.</p><p><strong>Conclusion: </strong>In this summary, we provide an overview of potential drugs that could be used to treat Mpox and discuss the underlying biological processes of their actions.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"62-76"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ClpP Peptidase as a Plausible Target for the Discovery of Novel Antibiotics.","authors":"Smriti Bhardwaj, Kuldeep K Roy","doi":"10.2174/0113894501274958231220053714","DOIUrl":"10.2174/0113894501274958231220053714","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) to currently available antibiotics/drugs is a global threat. It is desirable to develop new drugs that work through a novel target(s) to avoid drug resistance. This review discusses the potential of the caseinolytic protease P (ClpP) peptidase complex as a novel target for finding novel antibiotics, emphasising the ClpP's structure and function. ClpP contributes to the survival of bacteria via its ability to destroy misfolded or aggregated proteins. In consequence, its inhibition may lead to microbial death. Drugs inhibiting ClpP activity are currently being tested, but no drug against this target has been approved yet. It was demonstrated that Nblocked dipeptides are essential for activating ClpP's proteolytic activity. Hence, compounds mimicking these dipeptides could act as inhibitors of the formation of an active ClpP complex. Drugs, including Bortezomib, Cisplatin, Cefmetazole, and Ixazomib, inhibit ClpP activation. However, they were not approved as drugs against the target because of their high toxicity, likely due to the presence of strong electrophiles in their warheads. The modifications of these warheads could be a good strategy to reduce the toxicity of these molecules. For instance, a boronate warhead was replaced by a chloromethyl ketone, and this new molecule was shown to exhibit selectivity for prokaryotic ClpP. A better understanding of the structure and function of the ClpP complex would benefit the search for compounds mimicking N-blocked dipeptides that would inhibit ClpP complex activity and cause bacterial death.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"108-120"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}