Current drug targets最新文献_第10页

Revolutionizing Skin Cancer Treatment: The Rise of PD-1/PDL-1 and CTLA-4 as Key Therapeutic Targets. 皮肤癌治疗的革命：PD-1/PDL-1和CTLA-4作为关键治疗靶点的崛起。

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501320281240822052657

Neha Sharma, Rupa Mazumder, Pallavi Rai

{"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":"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.","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}

引用次数: 0

Breaking Barriers: Current Advances and Future Directions in Mpox Therapy. 打破障碍：麻疹治疗的当前进展和未来方向。

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501281263231218070841

Bhumi M Shah, Palmi Modi

{"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":"Background: 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.Objective: 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.Results: 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.Conclusion: 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.","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}

引用次数: 0

Multi-target Compounds against Trypanosomatid Parasites and Mycobacterium tuberculosis. 针对锥虫寄生虫和结核分枝杆菌的多靶点化合物。

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501306843240606114854

Midiane Correia Gomes, Emanuelly Karla Araújo Padilha, Gustavo Rafael Angelo Diniz, Edilma Correia Gomes, Paulo Fernando da Silva Santos-Júnior, Peng Zhan, Edeildo Ferreira da Siva-Júnior

引用次数: 0

Multitarget Compounds for Neglected Diseases: A Review. 治疗被忽视疾病的多靶点化合物：综述。

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501298864240627060247

Natália Ferreira de Sousa, Gabriela Ribeiro de Sousa, Natanael Teles Ramos de Lima, Edileuza Bezerra de Assis, Mariana Costa Aragão, Érika Paiva de Moura, Rajiv Gandhi Gopalsamy, Marcus Tullius Scotti, Luciana Scotti

{"title":"Multitarget Compounds for Neglected Diseases: A Review.","authors":"Natália Ferreira de Sousa, Gabriela Ribeiro de Sousa, Natanael Teles Ramos de Lima, Edileuza Bezerra de Assis, Mariana Costa Aragão, Érika Paiva de Moura, Rajiv Gandhi Gopalsamy, Marcus Tullius Scotti, Luciana Scotti","doi":"10.2174/0113894501298864240627060247","DOIUrl":"10.2174/0113894501298864240627060247","url":null,"abstract":"Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety. Thus, the objective of our study is to evaluate existing multitarget compound approaches for neglected diseases, with an emphasis on Leishmaniasis, Chagas Disease, and Arboviruses. A literature review was performed by searching the database \"Web of Sciences\". In relation to the diseases covered in this work, Leishmaniasis, individually, was the one that presented the largest number of articles (11) that dealt with the topic, which can be justified by the high prevalence of this disease in the world, the second most common disease was Dengue, followed by Chagas disease, Chikungunya virus, and Zika virus. Furthermore, the multitarget potential of phenolic compounds was observed in all diseases under study, with the mechanisms related to the nucleus and transcription being the most reported mechanisms. From this perspective, it is worth highlighting the effectiveness of approaches related to multitarget drugs in discovering new therapeutic agents for neglected diseases.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"577-601"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533891","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}

引用次数: 0

ClpP Peptidase as a Plausible Target for the Discovery of Novel Antibiotics. 将 ClpP 肽酶作为发现新型抗生素的合理靶点。

IF 3.2 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501274958231220053714

Smriti Bhardwaj, Kuldeep K Roy

{"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":"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.","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}

引用次数: 0

Xerostomia: Advances and Challenges in Drug Development. 口腔干燥症：药物开发的进展与挑战》。

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501293941240228050343

Yoon-Jung Kim

引用次数: 0

Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement. 治疗术后疼痛的新靶点和药物传递系统:最新研究和临床进展。

IF 3.2 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501271207231127063431

Trilochan Satapathy, Gulab Singh, Ravindra Kumar Pandey, Shiv Shankar Shukla, Shiv Kumar Bhardwaj, Beena Gidwani

{"title":"Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement.","authors":"Trilochan Satapathy, Gulab Singh, Ravindra Kumar Pandey, Shiv Shankar Shukla, Shiv Kumar Bhardwaj, Beena Gidwani","doi":"10.2174/0113894501271207231127063431","DOIUrl":"10.2174/0113894501271207231127063431","url":null,"abstract":"Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"25-45"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458418","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}

引用次数: 0

Efficacy and Possible Mechanisms of Astragali Radix and its Ingredients in Animal Models of Osteoporosis: A Preclinical Review and Metaanalysis. 黄芪及其成分在骨质疏松症动物模型中的疗效和可能机制：临床前综述与元分析》。

IF 3.2 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501275292231220062838

Ning Cao, Zhangxuan Shou, Yi Xiao, Puqing Liu

{"title":"Efficacy and Possible Mechanisms of Astragali Radix and its Ingredients in Animal Models of Osteoporosis: A Preclinical Review and Metaanalysis.","authors":"Ning Cao, Zhangxuan Shou, Yi Xiao, Puqing Liu","doi":"10.2174/0113894501275292231220062838","DOIUrl":"10.2174/0113894501275292231220062838","url":null,"abstract":"Background: Astragali Radix (AR) has a long history as a traditional Chinese medicine for anti-osteoporosis (OP) treatment. The aim of the study was to explore the effect and optimal regimens of AR and its main ingredients (IAR) in OP treatment.Methods: Eligible animal studies were searched in seven databases (PubMed, Web of Science, MEDLINE, SciELO Citation Index, Cochrane Library, China National Knowledge Infrastructure and Wanfang). The primary outcomes were bone metabolic indices. The secondary outcome measure was the anti-OP mechanism of IAR.Results: 21 studies were enrolled in the study. The primary findings of the present article illustrated that IAR could significantly increase the bone mineral density (BMD), bone volume over the total volume, trabecular number, trabecular thickness, bone maximum load and serum calcium, while trabecular separation and serum C-terminal telopeptide of type 1 collagen were remarkably decreased (P < 0.05). In subgroup analysis, the BMD in the long treatment group (≥ 10 weeks) showed better effect size than the short treatment group (< 10 weeks) (P < 0.05). Modeling methods and animal sex were factors affecting serum alkaline phosphatase and osteocalcin levels.Conclusion: The findings suggest the possibility of developing IAR as a drug for the treatment of OP. IAR with longer treatment time may achieve better effects regardless of animal strain and age.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"135-148"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424489","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}

引用次数: 0

Recent Progress and Challenges in Clinical Translation of Nanomedicines in Diagnosis and Treatment of Lung Cancer. 纳米药物在肺癌诊治中的临床转化研究进展与挑战。

IF 3.2 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501273651231201061144

Bhavna Yadav, Mahima Chauhan, Rahul Pratap Singh, Sonali, Saurabh Shekhar

{"title":"Recent Progress and Challenges in Clinical Translation of Nanomedicines in Diagnosis and Treatment of Lung Cancer.","authors":"Bhavna Yadav, Mahima Chauhan, Rahul Pratap Singh, Sonali, Saurabh Shekhar","doi":"10.2174/0113894501273651231201061144","DOIUrl":"10.2174/0113894501273651231201061144","url":null,"abstract":"Lung cancer is one of the leading causes of death across the world. There are numerous challenges in the early diagnosis and effective treatment of lung cancer, including developing multidrug resistance. However, the diagnosis of lung cancer could be minimally invasive or non-invasive. Nowadays, nanomedicines offer solutions to several emerging challenges in drug delivery research areas. It has the potential to enhance the therapeutic efficacy of biologically and chemically active agents at the site of action. This approach can also be employed in molecular and cellular imaging, precise and early detection, screening, and targeting drugs for lung cancer treatment. A proper understanding of the disease and timely diagnosis using strategically designed effective nanocarriers can be a promising approach to effectively managing cancer. The present review explores issues related to lung cancer chemotherapy and the promises and hurdles of newer approaches like nanomedicine. The article also summarizes the preclinical studies on diagnosis and treatment, pitfalls, and challenges in the clinical translation of nanomedicines for lung cancer therapy.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"12-24"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498024","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}

引用次数: 0

Therapeutic Correlation of TLR-4 Mediated NF-κB Inflammatory Pathways in Ischemic Injuries. 缺血性损伤中 TLR-4 介导的 NF-κB 炎症通路的治疗相关性

IF 3 4区医学

Current drug targets Pub Date : 2024-01-01 DOI: 10.2174/0113894501322228240830063605

Veerta Sharma, Prateek Sharma, Thakur Gurjeet Singh

{"title":"Therapeutic Correlation of TLR-4 Mediated NF-κB Inflammatory Pathways in Ischemic Injuries.","authors":"Veerta Sharma, Prateek Sharma, Thakur Gurjeet Singh","doi":"10.2174/0113894501322228240830063605","DOIUrl":"10.2174/0113894501322228240830063605","url":null,"abstract":"Ischemia-reperfusion (I/R) injury refers to the tissue damage that happens when blood flow returns to tissue after a period of ischemia. I/R injuries are implicated in a large array of pathological conditions, such as cerebral, myocardial, renal, intestinal, retinal and hepatic ischemia. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as significant contributors to inflammation caused by pathogens and, more recently, inflammation caused by injury. TLR-4 activation initiates a series of events that results in activation of nuclear factor kappa-B (NF-κB), which stimulates the production of pro-inflammatory cytokines and chemokines, exacerbating tissue injury. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the TLRs signalling pathway and the role of TLR-4/NF-κB in the pathophysiology of I/R injuries. Furthermore, this review highlights the various pharmacological agents (TLR-4/NF-κB inhibitors) with special emphasis on the various ischemic injuries (cerebral, myocardial, renal, intestinal, retinal and hepatic). Future research should prioritise investigating the specific molecular pathways that cause TLR-4/NF-κBmediated inflammation in ischemic injuries. Additionally, efforts should be made to enhance treatment approaches in order to enhance patient outcomes.","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":"1027-1040"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281661","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}

引用次数: 0