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Journal articles on the topic 'Clinical trials; drug discovery; drug repurp'

Author: Grafiati

Published: 2 June 2025

Last updated: 31 July 2025

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1

Sakshi, Kaushik* Priyal Jain. "Drug Repurposing an Effective Tool in Modern Drug Discovery." International Journal of Pharmaceutical Sciences 3, no. 5 (2025): 2652–56. https://doi.org/10.5281/zenodo.15432771.

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Drug repurposing is using an existing drug for a new treatment that was not indicated before. It has received immense attention during theCOVID-19 pandemic emergency. Drug repurposing has become the need of time to fasten the drug discovery process and find quickersolutionsto the over- exerted healthcare scenario and drug needs. Drug repurposing involve side notifying the drug, evaluatingits efficiency using preclinical models, and proceeding to phase II clinical trials. Identification of the drug candidate can be made through computational and experimental approaches. This approach usually ut

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Galustian, Christine, and Angus G. Dalgleish. "Article Commentary: The Power of the Web in Cancer Drug Discovery and Clinical Trial Design: Research without a Laboratory?" Cancer Informatics 9 (January 2010): CIN.S3191. http://dx.doi.org/10.4137/cin.s3191.

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The discovery of effective cancer treatments is a key goal for pharmaceutical companies. However, the current costs of bringing a cancer drug to the market in the USA is now estimated at $1 billion per FDA approved drug, with many months of research at the bench and costly clinical trials. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies and lower costs.

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Płocinska, Renata, Malgorzata Korycka-Machala, Przemyslaw Plocinski, and Jaroslaw Dziadek. "Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery." Current Topics in Medicinal Chemistry 17, no. 19 (2017): 2129–42. http://dx.doi.org/10.2174/1568026617666170130114342.

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Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and th

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Kawabata, Shinji, Hiroyuki Nakamura, Kohei Tsujino, et al. "10112- ET-10 EVALUATING PBC-IP AS A NOVEL BORON CARRIER IN BNCT." Neuro-Oncology Advances 6, Supplement_4 (2024): iv5. http://dx.doi.org/10.1093/noajnl/vdae173.019.

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Abstract This study aims to expand the application scope of boron neutron capture therapy (BNCT) for BPA-insensitive cancers. To apply BNCT in the treatment of brain tumors, convection-enhanced delivery (CED) is used as the drug administration method. CED is expected to enhance therapeutic efficacy by delivering drugs directly to tumor tissues. Therefore, the development of BNCT necessitates planning non-clinical trials from both pharmaceutical and medical device perspectives, including tests on standards, quality, and safety for clinical trial implementation. Previous investigations have demo

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Owen, Dafydd R., Charlotte M. N. Allerton, Annaliesa S. Anderson, et al. "An oral SARS-CoV-2 M ^pro inhibitor clinical candidate for the treatment of COVID-19." Science 374, no. 6575 (2021): 1586–93. http://dx.doi.org/10.1126/science.abl4784.

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Path to another drug against COVID-19 The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al . report the discovery and characterization of a drug against

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Rabinowitz, J. "What do Clinical Trials Tell us About Antidepressant Delayed Onset of Action?" European Psychiatry 41, S1 (2017): S3—S4. http://dx.doi.org/10.1016/j.eurpsy.2017.01.018.

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Response to antidepressants in major depressive disorder is highly variable and determinants are not well understood. Presentation will provide clinical trial data on time to response and determinants of response to antidepressant treatment. Data is from the Innovative Medicines Initiative funded NEWMEDS collaboration, a large public-private collaboration which assembled the largest dataset of individual patient level information from randomized placebo-controlled trials of antidepressant drugs. Studies were conducted by four large pharmaceutical companies. Dataset includes placebo-controlled

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Kimmelman, Jonathan. "Ethics at Phase 0: Clarifying the Issues." Journal of Law, Medicine & Ethics 35, no. 4 (2007): 727–33. http://dx.doi.org/10.1111/j.1748-720x.2007.00194.x.

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Many commentators have expressed concern that large investments in biomedical research over the past two decades have not been translated effectively into clinical applications. In its Critical Path Report, the Food and Drug Administration (FDA) characterized the problem as a “technological disconnect between discovery and the product development process,” and documented that the number of investigational new drugs (INDs) submitted to the agency had declined “significantly” since 2000. Along a similar vein, another study found that only five of 101 basic science studies showing significant the

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Bonaventura, Gabriele, Rosario Iemmolo, Giuseppe Antonino Attaguile, et al. "iPSCs: A Preclinical Drug Research Tool for Neurological Disorders." International Journal of Molecular Sciences 22, no. 9 (2021): 4596. http://dx.doi.org/10.3390/ijms22094596.

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The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all step

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Grossman, Stuart, Carlos Romo, Michelle Rudek-Renaut, et al. "ACTR-58. BASELINE REQUIREMENTS FOR NOVEL AGENTS BEING CONSIDERED FOR BRAIN CANCER EFFICACY TRIALS: REPORT OF AN ABTC WORKSHOP." Neuro-Oncology 21, Supplement_6 (2019): vi27. http://dx.doi.org/10.1093/neuonc/noz175.100.

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Abstract Despite advances in the understanding of molecular pathways, the availability of NGS panels to identify potentially drugable mutations, the proliferation of targeted therapies, and the progress seen in other cancers, only one novel agent (temozolomide) has significantly improved the survival of patients with glioblastoma in the past three decades. A major factor distinguishing brain cancer from other malignancies is the presence of the blood-brain barrier that restricts entry into the central nervous system of over 95% of drugs currently approved by the FDA. Clinical investigators hav

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Mohapatra, Sovesh, Prathul Nath, Manisha Chatterjee, et al. "Repurposing therapeutics for COVID-19: Rapid prediction of commercially available drugs through machine learning and docking." PLOS ONE 15, no. 11 (2020): e0241543. http://dx.doi.org/10.1371/journal.pone.0241543.

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Background The outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus has spread rapidly around the globe during the past 3 months. As the virus infected cases and mortality rate of this disease is increasing exponentially, scientists and researchers all over the world are relentlessly working to understand this new virus along with possible treatment regimens by discovering active therapeutic agents and vaccines. So, there is an urgent requirement of new and effective medications that can treat the disease caused by SARS-CoV-2. Methods and findings We perform the s

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Buckley, Lorrene A., Ilona Bebenek, Paul D. Cornwell, et al. "Drug Development 101: A Primer." International Journal of Toxicology 39, no. 5 (2020): 379–96. http://dx.doi.org/10.1177/1091581820939083.

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Drug development is a term used to define the entire process of bringing a new drug or device to market. It is an integrated, multidisciplinary endeavor that includes drug discovery, chemistry and pharmacology, nonclinical safety testing, manufacturing, clinical trials, and regulatory submissions. This report summarizes presentations of a workshop entitled “Drug Development 101,” held at the 39th Annual Meeting of the American College of Toxicology in West Palm Beach, Florida. The workshop was designed to provide an introductory overview of drug development. Experienced scientists from industr

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Castanheira, Lígia, Miguel F. Ferreira, Ana M. Sebastião, and Diogo Telles-Correia. "Anxiety Assessment in Pre-clinical Tests and in Clinical Trials: A Critical Review." Current Topics in Medicinal Chemistry 18, no. 19 (2018): 1656–76. http://dx.doi.org/10.2174/1568026618666181115102518.

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The identification of anxious symptoms is crucial to diagnose anxiety disorders, as well as to monitor their treatment in clinical practice and research. The aim of this review is to discuss the different ways of assessing anxiety in clinical research, including clinical trials, and the different kinds of animal behavioral tests used to study anxiety and test the efficacy of anxiolytics in pre-clinical studies. In clinical practice, a categorical classification (such as the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Re

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Koons, Natalie, Nicole Amato, Scott Sauer, David Warshawsky, Dalit Barkan, and Chand Khanna. "Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis." Pharmaceuticals 14, no. 10 (2021): 971. http://dx.doi.org/10.3390/ph14100971.

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Osteosarcoma (OS) is an aggressive mesenchymal cell tumor that carries a poor long-term prognosis. Despite definitive surgery for the primary tumor and adjuvant chemotherapy, pulmonary metastasis is common and is the primary cause of morbidity. To improve outcomes for patients, we have developed and optimized a phenotypic screen for drugs that may target OS disseminated tumor cells (DTCs) and inhibit their metastatic outbreak rather than merely screening for cytotoxic activity against proliferating cells, as is commonly conducted in conventional drug discovery approaches. We report on the vali

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Cicciù, Fiorillo, and Cervino. "Chitosan Use in Dentistry: A Systematic Review of Recent Clinical Studies." Marine Drugs 17, no. 7 (2019): 417. http://dx.doi.org/10.3390/md17070417.

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This study aims to highlight the latest marine-derived technologies in the biomedical field. The dental field, in particular, uses many marine-derived biomaterials, including chitosan. Chitosan that is used in different fields of medicine, is analyzed in this review with the aim of highlighting its uses and advantages in the dental field. A literature search was conducted in scientific search engines, using keywords in order to achieve the highest possible number of results. A review of randomized controlled trials (RCT) was conducted to evaluate and process all the relevant results for chitos

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Das, Moumita, Nihar Ranjan Panda, Ruchi Bhuyan, and Sanat Kumar Bhuyan. "Moringa oleifera and its application in dental conditions: A systematic review and meta-analysis." Journal of Herbmed Pharmacology 12, no. 3 (2023): 331–36. http://dx.doi.org/10.34172/jhp.2023.35.

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Moringa oleifera is a considerable ethnomedical herb with various bioactive compounds. This study aimed to analyze the efficacy of M. oleifera in the prevention and management of various oral conditions. A thorough search was conducted on the Web of Science, Scopus, PubMed, and PubMed Central databases. After screening the data on the basis of inclusion and exclusion criteria, 9 studies were considered for further meta-analysis. The analysis was performed on R programming software (version R-4.0.2) and the results were represented by a forest plot. The estimate obtained via common and random e

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Marchesi, Francesco, Corrado Girmenia, Bianca Maria Goffredo, et al. "Isavuconazole: Case Report and Pharmacokinetic Considerations." Chemotherapy 63, no. 5 (2018): 253–56. http://dx.doi.org/10.1159/000494329.

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Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom t

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Husnain, Ali, Saad Rasool, Ayesha Saeed, and Hafiz Khawar Hussain. "Revolutionizing Pharmaceutical Research: Harnessing Machine Learning for a Paradigm Shift in Drug Discovery." International Journal of Multidisciplinary Sciences and Arts 2, no. 2 (2023): 149–57. http://dx.doi.org/10.47709/ijmdsa.v2i2.2897.

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The fusion of machine learning (ML) and artificial intelligence (AI) is experiencing a dramatic transition in the field of pharmaceutical research and development. This study examines the several effects of machine learning (ML) on different phases of medication discovery, development, and patient care. The capability of ML to quickly process huge chemical libraries and forecast interactions with target proteins is studied, starting with compound screening and selection. The potential for fewer false positives and negatives, improved hit prediction accuracy, and ensemble technique use are unde

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Awasthi, Shivangi, Daniel S. Spellman, and Nathan G. Hatcher. "Proteomic Discovery and Validation of Novel Fluid Biomarkers for Improved Patient Selection and Prediction of Clinical Outcomes in Alzheimer’s Disease Patient Cohorts." Proteomes 10, no. 3 (2022): 26. http://dx.doi.org/10.3390/proteomes10030026.

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Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive decline. The two cardinal neuropathological hallmarks of AD include the buildup of cerebral β amyloid (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau. The current disease-modifying treatments are still not effective enough to lower the rate of cognitive decline. There is an urgent need to identify early detection and disease progression biomarkers that can facilitate AD drug development. The current established readouts based on the expression levels of amyloid beta,

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Dri, Diego Alejandro, Giulia Praticò, Elisa Gaucci, Carlotta Marianecci, and Donatella Gramaglia. "Quality Assessment of Investigational Medicinal Products in COVID-19 Clinical Trials: One Year of Activity at the Clinical Trials Office." Pharmaceuticals 14, no. 12 (2021): 1321. http://dx.doi.org/10.3390/ph14121321.

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One year after the spread of the pandemic, we analyzed the assessment results of the quality documentation submitted to the Clinical Trials Office of the Italian Medicines Agency as part of the request for authorization of clinical trials with a COVID-19 indication. In this article, we report the classification of the documentation type, an overview of the assessment results, and the related issues focusing on the most frequently detected ones. Relevant data regarding the Investigational Medicinal Products (IMPs) tested in COVID-19 clinical trials and their quality profiles are provided in the

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Saide, Assunta, Chiara Lauritano, and Adrianna Ianora. "Pheophorbide a: State of the Art." Marine Drugs 18, no. 5 (2020): 257. http://dx.doi.org/10.3390/md18050257.

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Chlorophyll breakdown products are usually studied for their antioxidant and anti-inflammatory activities. The chlorophyll derivative Pheophorbide a (PPBa) is a photosensitizer that can induce significant anti-proliferative effects in several human cancer cell lines. Cancer is a leading cause of death worldwide, accounting for about 9.6 million deaths, in 2018 alone. Hence, it is crucial to monitor emergent compounds that show significant anticancer activity and advance them into clinical trials. In this review, we analyze the anticancer activity of PPBa with or without photodynamic therapy an

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Della Sala, Gerardo, Francesca Agriesti, Carmela Mazzoccoli, Tiziana Tataranni, Valeria Costantino, and Claudia Piccoli. "Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update." Marine Drugs 16, no. 12 (2018): 467. http://dx.doi.org/10.3390/md16120467.

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The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory and misfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites

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Demeulemeester, Jonas, Cristina Tintori, Maurizio Botta, Zeger Debyser, and Frauke Christ. "Development of an AlphaScreen-Based HIV-1 Integrase Dimerization Assay for Discovery of Novel Allosteric Inhibitors." Journal of Biomolecular Screening 17, no. 5 (2012): 618–28. http://dx.doi.org/10.1177/1087057111436343.

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In recent years, HIV-1 integrase (IN) has become an established target in the field of antiretroviral drug discovery. However, its sole clinically approved inhibitor, the integrase strand transfer inhibitor (INSTI) raltegravir, has a surprisingly low genetic barrier for resistance. Furthermore, the only two other integrase inhibitors currently in advanced clinical trials, elvitegravir and dolutegravir, share its mechanism of action and certain resistance pathways. To maintain a range of treatment options, drug discovery efforts are now turning toward allosteric IN inhibitors, which should be d

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Svensen, Nina, Susan Wyllie, David W. Gray, and Manu De Rycker. "Live-imaging rate-of-kill compound profiling for Chagas disease drug discovery with a new automated high-content assay." PLOS Neglected Tropical Diseases 15, no. 10 (2021): e0009870. http://dx.doi.org/10.1371/journal.pntd.0009870.

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Chagas disease, caused by the protozoan intracellular parasite Trypanosoma cruzi, is a highly neglected tropical disease, causing significant morbidity and mortality in central and south America. Current treatments are inadequate, and recent clinical trials of drugs inhibiting CYP51 have failed, exposing a lack of understanding of how to translate laboratory findings to the clinic. Following these failures many new model systems have been developed, both in vitro and in vivo, that provide improved understanding of the causes for clinical trial failures. Amongst these are in vitro rate-of-kill

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Wang, Gan, Meng-Li Yang, Zi-Lei Duan, et al. "Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models." Cell Research 31, no. 1 (2020): 17–24. http://dx.doi.org/10.1038/s41422-020-00450-0.

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AbstractInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2)

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Habchi, Johnny, Paolo Arosio, Michele Perni та ін. "An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer’s disease". Science Advances 2, № 2 (2016): e1501244. http://dx.doi.org/10.1126/sciadv.1501244.

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The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer’s disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials with these objectives have so far failed, at least in part because of a lack of understanding of the molecular mechanisms underlying the process of aggregation and its inhibition. To address this problem, we describe a chemical kinetics approach for rational drug discovery, in which the effects of

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Patwardhan, Chaitanya A., Eyad Alfa, Su Lu, and Ahmed Chadli. "Progesterone Receptor Chaperone Complex–Based High-Throughput Screening Assay." Journal of Biomolecular Screening 20, no. 2 (2014): 223–29. http://dx.doi.org/10.1177/1087057114549147.

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Hsp90 and its co-chaperones are known to be important for cancer cell survival. The N-terminal inhibitors of Hsp90 that are in ongoing clinical trials as antitumor agents have unfortunately shown disappointing efficacies in the clinic. Thus, novel inhibitors of the Hsp90 machine with a different mechanism of action are urgently needed. We report here the development of a novel high-throughput screening assay platform to identify small-molecule inhibitors of Hsp90 and its co-chaperones. This assay quantitatively measures the ability of Hsp90 and its co-chaperones to refold/protect the progester

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Gklinos, Panagiotis, and Dimos Mitsikostas. "The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions." Pharmaceuticals 14, no. 3 (2021): 245. http://dx.doi.org/10.3390/ph14030245.

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Galcanezumab is a humanized monoclonal antibody blocking the calcitonin gene-related peptide (CGRP) pathway by targeting the CGRP. Data from four phase-3 randomized placebo-controlled clinical trials showed that galcanezumab is superior to placebo in reducing migraine headaches, migraine-specific quality of life, and headache-related disability. Most of the adverse events (AEs) were mild to moderate and did not affect trial completion rates significantly. Along with erenumab, fremanezumab, and eptinezumab, galcanezumab forms a novel class of anti-migraine preventative treatments that is diseas

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Lou, Xiaoxia, Wenfeng Li, Mend Pang, Yanqiang Wang, Xinli Zhu, and Jianhong Geng. "Clinical characterization of IRF2BPL mutation: Case series and review of the literature." Medicine 104, no. 1 (2025): e41078. https://doi.org/10.1097/md.0000000000041078.

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Rationale: IRF2BPL is an intronless gene localized to chromosome 14q24.3 that encodes an interferon regulatory factor 2 binding-like protein. In this study, we reviewed the literature on mutations in the IFR2BPL gene. In addition, we report a case of Neurodevelopmental Disorder with Degeneration, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) caused by a mutation in the IFR2BPL gene. The aim of this report is to increase clinicians’ awareness of such clinical cases. Patient concerns: In this report, we discuss the case of a 15-year-old male patient. The patient started with epilepsy

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Sagiv, Eyal, and Michael A. Portman. "CD24 for Cardiovascular Researchers: A Key Molecule in Cardiac Immunology, Marker of Stem Cells and Target for Drug Development." Journal of Personalized Medicine 11, no. 4 (2021): 260. http://dx.doi.org/10.3390/jpm11040260.

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The study of the membrane protein, CD24, and its emerging role in major disease processes, has made a huge leap forward in the past two decades. It appears to have various key roles in oncogenesis, tumor progression and metastasis, stem cell maintenance and immune modulation. First described in the 1980s as the homologous human protein to the mouse HSA (Heat Stable Antigen), it was reported as a surface marker in developing hematopoietic cell lines. The later discovery of its overexpression in a large number of human neoplasms, lead cancer researchers to discover its various active roles in cr

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Saxena, Anil K., and Muneer Alam. "ATP Synthase Inhibitors as Anti-tubercular Agents: QSAR Studies in Novel Substituted Quinolines." Current Topics in Medicinal Chemistry 20, no. 29 (2020): 2723–34. http://dx.doi.org/10.2174/1568026620666200903163515.

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Background: Tuberculosis (TB) is a major infectious disease caused by Mycobacterium Tuberculosis. As per the World Health Organization (WHO) report of 2019, there were 1.5 million deaths in the year 2018, mainly because of multi- and extensively drug-resistant tuberculosis (MDR & XDR-TB). Among several antitubercular drugs in clinical trials, bedaquiline (TMC207) is a highly promising drug that was approved by the FDA in 2012 and marketed in 2016 for the treatment of multidrug resistant TB in combination with other drugs. Bedaquiline acts on mycobacterial ATP synthase and is highly effecti

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Jahangir, Mohammed Asadullah, Mohamad Taleuzzaman, Chandra Kala, and Sadaf Jamal Gilani. "Advancements in Polymer and Lipid-based Nanotherapeutics for Cancer Drug Targeting." Current Pharmaceutical Design 26, no. 40 (2020): 5119–27. http://dx.doi.org/10.2174/1381612826999200820173253.

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Cancer is a global disease. It is the second leading cause of death worldwide, according to the health report. Approximately 70% of deaths from cancer occurs in low- and middle-income countries. According to the WHO, in 2015 8.8 million deaths were reported due to cancer worldwide. The conventional system of medicine was used since a long for the management of the disease, but it comes with the drawback of low safety, less efficacy and non-targeting of cancer cells. Nanotherapeutics has become the most exploited drug targeting system based on the safety and efficacy this system provides over t

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Weisberg, Ellen, Johannes Roesel, Guido Bold, et al. "Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells." Blood 112, no. 13 (2008): 5161–70. http://dx.doi.org/10.1182/blood-2008-02-138065.

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Abstract An attractive target for therapeutic intervention is constitutively activated, mutant FLT3, which is expressed in a subpopulation of patients with acute myelocyic leukemia (AML) and is generally a poor prognostic indicator in patients under the age of 65 years. PKC412 is one of several mutant FLT3 inhibitors that is undergoing clinical testing, and which is currently in late-stage clinical trials. However, the discovery of drug-resistant leukemic blast cells in PKC412-treated patients with AML has prompted the search for novel, structurally diverse FLT3 inhibitors that could be altern

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Bernard, Amandine, Aurore Danigo, Sylvie Bourthoumieu, et al. "The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management." Pharmaceuticals 14, no. 11 (2021): 1185. http://dx.doi.org/10.3390/ph14111185.

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Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our

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Barresi, Elisabetta, Marco Robello, Emma Baglini, et al. "Indol-3-ylglyoxylamide as Privileged Scaffold in Medicinal Chemistry." Pharmaceuticals 16, no. 7 (2023): 997. http://dx.doi.org/10.3390/ph16070997.

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In recent years, indolylglyoxylamide-based derivatives have received much attention due to their application in drug design and discovery, leading to the development of a wide array of compounds that have shown a variety of pharmacological activities. Combining the indole nucleus, already validated as a “privileged structure,” with the glyoxylamide function allowed for an excellent template to be obtained that is suitable to a great number of structural modifications aimed at permitting interaction with specific molecular targets and producing desirable therapeutic effects. The present review

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Belli, Stefania, Daniela Esposito, Alberto Servetto, Ada Pesapane, Luigi Formisano, and Roberto Bianco. "c-Src and EGFR Inhibition in Molecular Cancer Therapy: What Else Can We Improve?" Cancers 12, no. 6 (2020): 1489. http://dx.doi.org/10.3390/cancers12061489.

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The proto-oncogene c-Src is a non-receptor tyrosine kinase playing a key role in many cellular pathways, including cell survival, migration and proliferation. c-Src de-regulation has been observed in several cancer types, making it an appealing target for drug discovery efforts. Recent evidence emphasizes its crucial role not only in promoting oncogenic traits, but also in the acquisition and maintenance of cancer resistance to various chemotherapeutic or molecular target drugs. c-Src modulates epidermal growth factor receptor (EGFR) activation and amplifies its downstream oncogenic signals. I

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Kemboi, Douglas, Xolani Peter, Moses Langat, and Jacqueline Tembu. "A Review of the Ethnomedicinal Uses, Biological Activities, and Triterpenoids of Euphorbia Species." Molecules 25, no. 17 (2020): 4019. http://dx.doi.org/10.3390/molecules25174019.

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The genus Euphorbia is one of the largest genera in the spurge family, with diversity in range, distribution, and morphology. The plant species in this genus are widely used in traditional medicine for the treatment of diseases, ranging from respirational infections, body and skin irritations, digestion complaints, inflammatory infections, body pain, microbial illness, snake or scorpion bites, pregnancy, as well as sensory disorders. Their successes have been attributed to the presence of diverse phytochemicals like polycyclic and macrocyclic diterpenes with various pharmacological properties.

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Copmans, Daniëlle, Sara Kildgaard, Emma Roux, et al. "From the North Sea to Drug Repurposing, the Antiseizure Activity of Halimide and Plinabulin." Pharmaceuticals 15, no. 2 (2022): 247. http://dx.doi.org/10.3390/ph15020247.

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PharmaSea performed large-scale in vivo screening of marine natural product (MNP) extracts, using zebrafish embryos and larvae, to identify compounds with the potential to treat epilepsy. In this study, we report the discovery of two new antiseizure compounds, the 2,5-diketopiperazine halimide and its semi-synthetic analogue, plinabulin. Interestingly, these are both known microtubule destabilizing agents, and plinabulin could have the potential for drug repurposing, as it is already in clinical trials for the prevention of chemotherapy-induced neutropenia and treatment of non-small cell lung

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Eriksson, Anna, Albin Osterros, Sadia Hassan, et al. "Repositioning of Quinacrine for Treatment of Acute Myeloid Leukemia." Blood 124, no. 21 (2014): 3609. http://dx.doi.org/10.1182/blood.v124.21.3609.3609.

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Abstract Background: A promising strategy for new drug discovery is ‘repositioning’, in which a new indication for an existing drug is identified. Using this approach, known on-patent, off-patent, discontinued and withdrawn drugs with unrecognized cancer activity, can be rapidly advanced into clinical trials for the new indication. We here report findings from a library screen of pharmacologically active and mechanistically annotated compounds in leukemia cells from patients aiming at the identification of repositioning candidates. Methods and results: The LOPAC®, 1280substance library (Sigma-

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Campbell, Jessica, Juliet Sutherland, Danielle Bucknall, et al. "Equity in Vaccine Trials for Higher Weight People? A Rapid Review of Weight-Related Inclusion and Exclusion Criteria for COVID-19 Clinical Trials." Vaccines 9, no. 12 (2021): 1466. http://dx.doi.org/10.3390/vaccines9121466.

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Higher weight status, defined as body mass index (BMI) ≥ 30 kg/m2, is frequently described as a risk factor for severity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (known as COVID-19). Therefore, study groups in COVID-19 vaccine trials should be representative of the weight spectrum across the global population. Appropriate subgroup analysis should be conducted to ensure equitable vaccine outcomes for higher weight people. In this study, inclusion and exclusion criteria of registered clinical trial protocols were reviewed to determine the proport

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Santini-Oliveira, Marília, Patrícia Machado Pinto, Tatiane dos Santos, et al. "Development of the Sm14/GLA-SE Schistosomiasis Vaccine Candidate: An Open, Non-Placebo-Controlled, Standardized-Dose Immunization Phase Ib Clinical Trial Targeting Healthy Young Women." Vaccines 10, no. 10 (2022): 1724. http://dx.doi.org/10.3390/vaccines10101724.

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We report the successful closure of Phase I clinical trials, comprising Phases Ia and Ib, of the vaccine candidate against human schistosomiasis: the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE). Shown here are the results of Phase Ib, an open, non-placebo-controlled, standardized-dose immunization trial involving 10 healthy 18–49-year-old women. Fifty micrograms of the Sm14 protein plus 10 µg GLA-SE per dose was given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immu

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Santos, Lucianna H., Rafael E. O. Rocha, Diego L. Dias, et al. "Evaluating Known Zika Virus NS2B-NS3 Protease Inhibitor Scaffolds via In Silico Screening and Biochemical Assays." Pharmaceuticals 16, no. 9 (2023): 1319. http://dx.doi.org/10.3390/ph16091319.

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The NS2B-NS3 protease (NS2B-NS3pro) is regarded as an interesting molecular target for drug design, discovery, and development because of its essential role in the Zika virus (ZIKV) cycle. Although no NS2B-NS3pro inhibitors have reached clinical trials, the employment of drug-like scaffolds can facilitate the screening process for new compounds. In this study, we performed a combination of ligand-based and structure-based in silico methods targeting two known non-peptide small-molecule scaffolds with micromolar inhibitory activity against ZIKV NS2B-NS3pro by a virtual screening (VS) of promisi

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Chen, Xiaoxin, Qinhai Ma, Manyu Zhao, et al. "Preclinical Study of ZSP1273, a Potent Antiviral Inhibitor of Cap Binding to the PB2 Subunit of Influenza A Polymerase." Pharmaceuticals 16, no. 3 (2023): 365. http://dx.doi.org/10.3390/ph16030365.

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The influenza A virus is highly contagious and often causes global pandemics. The prevalence of strains of the influenza A virus that are resistant to approved drugs is a huge challenge for the current clinical treatment of influenza A. RNA polymerase is a pivotal enzyme in the replication of the influenza A virus, and it is a promising target for anti-influenza A therapies. In this paper, we report a novel and potent anti-influenza-A-virus inhibitor, ZSP1273, targeting the influenza A virus RNA polymerase, especially for multidrug-resistant strains. The inhibitory activity of ZSP1273 on RNA p

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Al-Hizab, Fahad, and Mahmoud Kandeel. "Mycophenolate suppresses inflammation by inhibiting prostaglandin synthases: a study of molecular and experimental drug repurposing." PeerJ 9 (April 30, 2021): e11360. http://dx.doi.org/10.7717/peerj.11360.

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Mycophenolate mofetil is an established anti-proliferative and immune-suppressive agent that minimizes the proliferation of inflammatory cells by interfering with nucleic acid synthesis. Herein, we report our discovery of the prostaglandin inhibiting properties of MMF, which offers new applications for the drug in the treatment of inflammatory diseases. The estimated values of IC50MMFCOX-1, IC50MMFCOX-2, and IC50MMF5-LOX were 5.53, 0.19, and 4.47 µM, respectively. In contrast, mycophenolic acid (MPA) showed slightly stronger inhibition: IC50MPACOX-1, IC50MPACOX-2, and IC50MPA5-LOX were 4.62, 0

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Prunotto, Marco, Patrick H. Nachman, Barbara S. Gillespie, et al. "Designing Clinical Trials for the Treatment of Membranous Nephropathy in the Anti-Phospholipase A2 Receptor 1 Era: Results of a NephCure Membranous Nephropathy Workshop." Glomerular Diseases 5, no. 1 (2025): 133–41. https://doi.org/10.1159/000544808.

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Primary membranous nephropathy is a common cause of adult-onset nephrotic syndrome, with an overall incidence of 12 cases per million per year. Primary membranous nephropathy is an autoimmune kidney disease; however, primary membranous nephropathy autoantigens remained elusive until 2009, when the M-type phospholipase A2 receptor 1 (PLA2R) was identified as a disease autoantigen. This was followed relatively rapidly by the identification of several other autoantigens. Autoantibodies against PLA2R are detectable in ≈75% of patients with primary membranous nephropathy. The discovery of circulati

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Ambili, R., K. Ramadas, Lekha M. Nair, et al. "Efficacy of a herbal mouthwash for management of periodontitis and radiation-induced mucositis – A consolidated report of two randomized controlled clinical trials." Journal of Ayurveda and Integrative Medicine 14, no. 6 (2023): 100791. http://dx.doi.org/10.1016/j.jaim.2023.100791.

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Shamsrizi, Parichehr, Frederik Johannes Kramer, Marylyn Martina Addo, and Anahita Fathi. "Characterization of Individuals Interested in Participating in a Phase I SARS-CoV-2 Vaccine Trial." Vaccines 9, no. 10 (2021): 1208. http://dx.doi.org/10.3390/vaccines9101208.

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The development of an effective vaccine against SARS-CoV-2 marks one of the highest priorities during the ongoing pandemic. However, recruitment of participants for clinical trials can be challenging, and recruitment failure is among the most common reasons for discontinuation in clinical trials. From 20 May 2020, public announcements about a planned phase I trial of the vaccine candidate MVA-SARS-2-S against SARS-CoV-2 began, and interested individuals started contacting the study team via designated e-mail. All emails received from these individuals between 20 May 2020–30 September 2020 were

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Feng, Wen-Han, Yong-Chieh Chang, Yi-Hsiung Lin, et al. "P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis." Pharmaceuticals 16, no. 2 (2023): 232. http://dx.doi.org/10.3390/ph16020232.

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P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) in the modern era. Clinical trials have shown that it could lower the risk of bleeding complications without increased ischemic events as compared to standard dual antiplatelet therapy (DAPT). However, the efficacy and safety of this novel approach among patients with acute coronary syndrome (ACS) are controversial because they have a much higher risk for recurrent ischemic events. The purpose of this study is to evaluate the efficacy and safety of this novel approach amo

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Tran, Linh Chi, Berna C. Özdemir, and Martin D. Berger. "The Role of Immune Checkpoint Inhibitors in Metastatic Pancreatic Cancer: Current State and Outlook." Pharmaceuticals 16, no. 10 (2023): 1411. http://dx.doi.org/10.3390/ph16101411.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, characterized by its aggressive tumor biology and poor prognosis. While immune checkpoint inhibitors (ICIs) play a major part in the treatment algorithm of various solid tumors, there is still no evidence of clinical benefit from ICI in patients with metastatic PDAC (mPDAC). This might be due to several reasons, such as the inherent low immunogenicity of pancreatic cancer, the dense stroma-rich tumor microenvironment that precludes an efficient migration of antitumoral effector T cells to the cancer cells, and the increase

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Prudden, Holly, Roger Tatoud, Cathy Slack, et al. "Experimental Medicine for HIV Vaccine Research and Development." Vaccines 11, no. 5 (2023): 970. http://dx.doi.org/10.3390/vaccines11050970.

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The development of safe and effective HIV vaccines has been a scientific challenge for more than 40 years. Despite disappointing results from efficacy clinical trials, much has been learnt from years of research and development. In a rapidly evolving HIV prevention landscape, swift evaluation of multiple vaccine approaches eliciting cross-reactive humoral and cellular responses is needed to ensure the development of efficacious vaccine candidates. To contain increasing costs, innovative clinical research methods are required. Experimental medicine has the potential to accelerate vaccine discov

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Magen, Eli, Sumit Mukherjee, Mahua Bhattacharya, et al. "Clinical and Molecular Characterization of a Rare Case of BNT162b2 mRNA COVID-19 Vaccine-Associated Myositis." Vaccines 10, no. 7 (2022): 1135. http://dx.doi.org/10.3390/vaccines10071135.

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Initial clinical trials and surveillance data have shown that the most commonly administered BNT162b2 COVID-19 mRNA vaccine is effective and safe. However, several cases of mRNA vaccine-induced mild to moderate adverse events were recently reported. Here, we report a rare case of myositis after injection of the first dose of BNT162b2 COVID-19 mRNA vaccine into the left deltoid muscle of a 34-year-old, previously healthy woman who presented progressive proximal muscle weakness, progressive dysphagia, and dyspnea with respiratory failure. One month after vaccination, BNT162b2 vaccine mRNA expres

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