Advances in pharmacology最新文献

{"title":"Phosphodiesterase 4 (PDE4) and neurological disorders: A promising frontier in neuropharmacology.","authors":"Sumaiya Nahid, Saeedeh Saeedi, Corey R Hopkins","doi":"10.1016/bs.apha.2024.10.005","DOIUrl":"10.1016/bs.apha.2024.10.005","url":null,"abstract":"<p><p>The phosphodiesterase 4 (PDE4) enzyme plays a crucial role in the central nervous system (CNS). It is extensively expressed in mammalian brain, where it regulates intracellular cyclic adenosine monophosphate (cAMP) levels. Dysregulation of PDE4 and cAMP balance is associated with various neurodegenerative diseases. By inhibiting PDE4 with drugs, cAMP levels can be stabilized, potentially improving symptoms in mental and neurological disorders such as cognition, depression, and Parkinson's disease. Mechanistically, PDE4 inhibitors exert anti-inflammatory and neuroprotective effects by increasing cAMP accumulation and activating protein kinase A (PKA). This chapter will review the relevant neurological disorders that PDE4 has been associated with and review the preclinical and clinical studies.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"102 ","pages":"159-209"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging horizons of AI in pharmaceutical research.","authors":"Sourav Bachhar, Suryasarathi Kumar, Basudeb Dutta, Somnath Das","doi":"10.1016/bs.apha.2025.01.016","DOIUrl":"10.1016/bs.apha.2025.01.016","url":null,"abstract":"<p><p>Artificial Intelligence (AI) has revolutionized drug discovery by enhancing data collection, integration, and predictive modeling across various critical stages. It aggregates vast biological and chemical data, including genomic information, protein structures, and chemical interactions with biological targets. Machine learning techniques and QSAR models are applied by AI to predict compound behaviors and predict potential drug candidates. Docking simulations predict drug-protein interactions, while virtual screening eliminates large chemical databases through efficient sifting. Similarly, AI supports de novo drug design by generating novel molecules, optimized against a particular biological target, using generative models such as generative adversarial network (GAN), always finding lead compounds with the most desirable pharmacological properties. AI used in clinical trials improves efficiency by pinpointing responsive patient cohorts leveraging genetic profiles and biomarkers and maintaining propriety such as dataset diversity and compliance with regulations. This chapter aimed to summarize and analyze the mechanism of AI to accelerate drug discovery by streamlining different processes that enable informed decisions and bring potential life-saving therapies to market faster, amounting to a breakthrough in pharmaceutical research and development.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"325-348"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacophore modeling in drug design.","authors":"Yasmin Momin, Vilas Beloshe","doi":"10.1016/bs.apha.2025.01.010","DOIUrl":"10.1016/bs.apha.2025.01.010","url":null,"abstract":"<p><p>A successful and expanded area of computational drug design is pharmacophore modeling. A pharmacophore is a description of the structural features of a compound that are essential to its biological activity. The rational design of new drugs has made extensive use of the pharmacophore concept. By schematically illustrating the essential components of molecular recognition, Pharmacophores can be used to represent and identify molecules in two or three dimensions. Besides target identification, the pharmacophore concept is also helpful for side effects, off-target, and absorption, distribution, and toxicity modeling. Moreover, to enhance virtual screening, pharmacophores, and molecular docking simulations are frequently coupled. A completely new area of drug design has been made possible by the development of machine learning techniques and pharmacophore mapping algorithms, wherein an ineffective molecule with the right modifications may have the potential to function as an inhibitor. This approach has been stimulated by its predictive abilities to assess the possibility that a set of compounds will be active against protein targets of interest. With alignment to the standard pharmacophore model, active compounds of the protein target can be developed. The pharmacophore modeling/screening technique is used to identify possible proteins of interest and seek out/suggest novel therapeutic uses for the drug.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"313-324"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-gen senotherapeutics: AI/ML-driven strategies for aging and age-related disorders.","authors":"Prashanth S Javali, Ashish Kumar, Subhajit Sarkar, R Sree Varshini, D Jose Mathew, Kavitha Thirumurugan","doi":"10.1016/bs.apha.2025.01.017","DOIUrl":"10.1016/bs.apha.2025.01.017","url":null,"abstract":"<p><p>Senotherapeutics comprising senolytics and senostats/senomorphs of natural and synthetic origin are powerful pharmacological interventions to combat aging and age-related disorders (ARD): cancer, HIV, diabetes, and neurodegenerative diseases. STs are novel strategies in the geroscience arena selectively targeting senescent cells responsible for unhealthy aging and ARD. The absence of specific biomarkers, gaps in integrating molecular mechanisms, and inadequate therapeutic drugs hamper translating the results from bench to bedside. Current innovations suggested to advance the field include machine learning, omics-based approaches, nanocarriers, molecularly imprinted nanoparticles, CART cells, and monoclonal antibodies. This book chapter will focus on STs interrupting molecular pathways involving senescent cells, SASPs, and immune cells in preclinical and clinical settings. Also, the chapter will highlight applications of AI/ML/DL tools like Random Forest, Support Vector Machines, phenotypic screening, neural networks, and predictive modeling for discovering STs to expedite the translation of preclinical findings to clinical applications. Despite challenges to obtaining quality data and model interpretability, the future of ML in senotherapeutics holds great promise in promoting longevity.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"87-119"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world application of molecular docking in drug discovery.","authors":"Somenath Dutta, Indrani Biswas, Subhabrata Goswami, Ananya Verma","doi":"10.1016/bs.apha.2025.01.013","DOIUrl":"10.1016/bs.apha.2025.01.013","url":null,"abstract":"<p><p>Computational drug designing comprising mainly Molecular Docking has surged in popularity due to its efficiency and precision in identifying potential therapeutic candidates, often collectively referred to as virtual screening. This method enables researchers to screen large compound libraries virtually, significantly speeding up the initial stages of drug development. The significance of molecular docking is particularly evident in the fight against rapidly evolving pathogens like SARS-CoV-2. Lately, the emergence of new COVID-19 variants, such as the highly transmissible XBB.1.5, is incessantly posing challenges. Conventional drug development approaches aimed on a single strain, outgazing the importance of virus' evolution which is well-facilitated by molecular docking that provides better assessment of therapeutic efficacy against multiple variants of this virus. In the present study, molecular docking was executed to screen potential phytochemicals against the spike protein XBB.1.5 variant, known for its critical mutations that enhance infectivity. As part of the entire screening protocol, other tools like Schrödinger's suite, SwissADME, and ProTox-II were utilized to identify the top leads. These computational facilitators assisted in estimation of binding affinity, pharmacokinetics and toxicity profiles. Estimation of these factors led to identification of promising lead compounds that depicted strong binding interactions against the mutated spike protein, suggesting their potential as broad-spectrum antiviral agents. The present study emphasizes the importance of computational tools and techniques like molecular docking in addressing the variants generated against continuous evolution of SARS-COV2. The methodologies adapted can be deployed against other disease towards development of targeted therapeutics, ensuring a proactive approach to global health threats.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"393-413"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in vaccine design: Computational tools and techniques.","authors":"Riya Nag, Sanchita Srivastava, Saliha Rizvi, Samar Ahmed, Syed Tasleem Raza","doi":"10.1016/bs.apha.2025.01.015","DOIUrl":"10.1016/bs.apha.2025.01.015","url":null,"abstract":"<p><p>The advancements in computational tools have revolutionized vaccine development by organizing and analyzing large-scale immunological data through immuno-informatics. This field combines computational and mathematical approaches to model molecular interactions during antigen presentation and processing. These tools have significantly accelerated vaccine development, making it more efficient and cost-effective. Applications such as SCWRL and SCAP help in side chain and backbone modeling to improve antibodies and forecast secondary structures. Multi-graft and multivalent scaffolds present antigens to elicit strong immune responses; antibodyomics studies the sequences of antibodies to find antibodies that can neutralize. It is another traditional way of doing vaccines where the pathogen's genome is scanned by diacide such as Vaxign to identify the likely vaccine agents. Codon optimization, as implemented with the aid of COOL and OPTIMIZER tools, enhances the output of proteins among which vaccines are needed. These tools also allow for predicting epitope structures the more accurately, or so. Prediction tools that include immunogenicity screening tests that map B-cell epitope and T-cell epitope such as ElliPro and DiscoTope aid in drug design, while the application of Fusion technologies facilitates vaccine development and kit diagnostics. The percentage of time trying to identify possible vaccine candidates is reduced alongside the costs with the application of these tools allowing the improvement in the prediction of vaccine candidates. The purpose of this chapter is to emphasize the invention of computational tools and methods that together are revolutionizing vaccine design and development and to underline the importance of tissue engineering and immunology advances.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"375-391"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senotherapeutics: Milestones, innovations, and future prospects.","authors":"Erdem Atasever, Mehmet Can Atayik, Ufuk Çakatay","doi":"10.1016/bs.apha.2025.01.021","DOIUrl":"10.1016/bs.apha.2025.01.021","url":null,"abstract":"<p><p>Gerontological practice has evolved over the decades in response to various diseases, comorbidities, and demographic factors. The many subfields that have emerged from our advancement include the study of biomedical gerontology. Geropharmacology, which began to be recognized as a distinct subfield in the latter part of the 20th century, is the study of how the elderly population responds to pharmaceutical interventions, considering the effects, interactions, and side effects, along with appropriate dosages and routes. In the past, aging has generally received negative coverage. \"Everyone wants to live longer, but no one wants to grow old.\" It is feared that old age will be rustier than gold. In recent decades, the importance of geropharmacology has increased due to the challenges we face in managing the elderly groups, alongside the growing elderly population, since these groups have altered pharmacokinetics and a higher number of comorbidities. Gerotherapeutics are pharmacological agents that can impede or decrease the rate of aging-related degenerative processes and extend lifespans by repairing damage or modulating stress resistance. Current research in the field of geropharmacology not only investigates the effects of existing conventional pharmacologic agents such as quercetin, rapamycin, aspirin, cardiac glycosides, metformin, and JAK inhibitors on the elderly population but also includes the development of new promising gerotherapeutics. AI-assisted senotherapeutic drug discovery is a continuing task in geropharmacology. No candidate drug with senescent cell targeting has yet been widely clinically tested since the senotherapeutic approach has many limitations in geriatric practice. Senescence, also, is a physiological process that continues throughout the lifespan and should not be viewed as only an effect of aging. Senescent cells found in different organs show heterogeneous phenotypes. Induction of senescence is initially a protective response that prevents older, damaged, or cancerous cells from replicating and causing further harm to the tissues. When discussing senotherapeutic medicines and their potential application in clinical practice, it is important to consider their nonspecific action on senescent cells, which may potentially aid in cancer prevention and stimulate processes related to wound healing.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen-ozone adjunct therapy in aging and senescence-related disorders. State of art.","authors":"Salvatore Chirumbolo, Giovanni Ricevuti, Marianno Franzini, Francesco Vaiano, Antonio Carlo Galoforo, Tommaso Richelmi, Umberto Tirelli, Luigi Valdenassi","doi":"10.1016/bs.apha.2025.03.001","DOIUrl":"10.1016/bs.apha.2025.03.001","url":null,"abstract":"<p><p>Ozone therapy presents as a promising yet controversial approach to anti-aging and health rejuvenation, due to an ongoing and crucially debated need for standardization about protocols, procedures, and dosages. While it offers potential benefits in improving skin health, boosting energy levels, and reducing inflammation, its use must be carefully considered only by specialized, highly trained experts and professionals, due to potential risks related to malpractice and shallow or clumsy fashion trends. The ability of ozone to address senescent mechanisms and aging-related processes makes this adjunct therapy a promising approach for aging-related impairments, such as neurodegenerative disorders and cardiovascular pathologies.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"417-446"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacy-induced changes in the oral mucosa and jawbone in elderly.","authors":"Sabahat Zeynep Yey Ozkeskin, Kaan Erisildar, Mehmet Yaltirik","doi":"10.1016/bs.apha.2025.02.008","DOIUrl":"10.1016/bs.apha.2025.02.008","url":null,"abstract":"<p><p>Polypharmacy is increasingly prevalent among the elderly due to the higher incidence of chronic diseases. The oral cavity undergoes age-related changes, including cellular aging and immunosenescence. Thus, susceptibility to oral discomfort increases in the elderly, and decreased salivary secretion, ulceration, burning sensations, and other oral symptoms can be seen. The oral mucosa is particularly vulnerable to conditions such as xerostomia, mucositis, and oral candidiasis, exacerbated by medications that impact salivary gland function and immune response. Key pharmacological agents implicated in these effects include antihypertensives, antidiabetics, bisphosphonates, and immunosuppressants. Although these medications are essential for the overall health of the patient, the long-term effects of polypharmacy on the oral cavity cannot be overlooked. Their impact on oral health necessitates careful consideration. A comprehensive understanding of oral changes is essential for developing strategies to mitigate the adverse effects of polypharmacy and improve oral health outcomes in the elderly. This chapter synthesizes existing research to identify causative agents and summarizes preventive measures, diagnostic criteria, and treatment strategies related to polypharmacy-induced oral mucosa and jawbone alterations. Furthermore, it outlines current research findings and provides recommendations for clinical practice, highlighting the importance of interdisciplinary collaboration in managing the oral health of elderly patients with complex medication regimens.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"447-473"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"Chaitanay Vinayak Narayan, Swati Verma, Ajmer Singh Grewal, Neelam Singh, Hemlata Nimesh","doi":"10.1016/S1054-3589(25)00060-2","DOIUrl":"https://doi.org/10.1016/S1054-3589(25)00060-2","url":null,"abstract":"","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"xxix-xxx"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}