Pharmaceutical Science Advances最新文献

{"title":"Biowaiver based on biopharmaceutics classification system: Considerations and requirements","authors":"Pratik R. Dhake ,&nbsp;Smita T. Kumbhar ,&nbsp;Vinod L. Gaikwad","doi":"10.1016/j.pscia.2023.100020","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100020","url":null,"abstract":"<div><p>Biowaiver allows for the waiver of bioequivalence studies for regulatory approval of certain drug products with saving of time, and money. Before approval of the application for biowaivers, studies based on the Biopharmaceutical Classification System (BCS) are required to satisfy regulators in the US, Europe, and other developing markets. Only pharmaceutical products that meet the regulatory requirements for solubility, diffusion, and permeability will be granted a biowaiver. Due to high solubility and considerable permeability, BCS class I and class III drugs are highly preferred for biowaiver by regulatory agencies. The World Health Organization recently expanded the scope of the biowaiver acceptance by considering all BCS classes. These techniques can cut down on time and money spent on ineffective bioequivalence studies. In the present article, an attempt has been made to cover the prerequisites and guidelines for biowaiver approval of a generic product, a topical system, oral films, and BCS class II and IV drugs.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000181/pdfft?md5=7157f3d3138990657264b234d0fabc3c&pid=1-s2.0-S2773216923000181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92150350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The most recent advances in liquisolid technology: Perspectives in the pharmaceutical industry","authors":"Yaseen Hussain ,&nbsp;Jinghao Cui ,&nbsp;Amos Dormocara ,&nbsp;Haroon Khan","doi":"10.1016/j.pscia.2024.100038","DOIUrl":"10.1016/j.pscia.2024.100038","url":null,"abstract":"<div><p>Hydrophobic drugs exhibit altered bioavailability and pose other challenges at an industrial level due to their poor solubility and dissolution rates. In addition, poor flowability, compressibility, complex dosing schedules, and light-sensitivity problems associated with hydrophobic drugs have led to poor patient compliance. To overcome these problems at an industrial level, the liquid-solid technique is a promising approach for tackling such challenges. This study outlines the prementioned challenges related to hydrophobic drug candidates and introduces the liquisolid technique as a potential alternative using non-volatile water-miscible solvents, carrier agents, coating substances, and their subsequent applications in the pharmaceutical industry. Furthermore, this study highlights the role of liquisolid technology in achieving sustained-release kinetics, emphasizing its benefits in minimizing pH changes in drug release and enhancing photostability. The study aimed to explore the liquisolid technique as an important tool for improving drug delivery, overcoming solubility issues, and optimizing therapeutic outcomes. In addition, this manuscript holds significant importance by highlighting the applications and recent advances in liquisolid technology, focusing on industrial-level applications. Moreover, it is impressive that such a technique offers improved formulation options to enhance the safety and efficacy of therapy. Overall, this study serves as a valuable resource for researchers to overcome formulation challenges and optimize drug delivery in the pharmaceutical industry.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000047/pdfft?md5=28e7fad4f3931f73de3aa176469437b7&pid=1-s2.0-S2773216924000047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrine induces V-ATPase-dependent cytoplasmic vacuolation and inhibits the function of the lysosome in leukemia cells","authors":"Fanfan Yang ,&nbsp;Wang-jing Zhong ,&nbsp;Jialin Cao ,&nbsp;Junyu Tan ,&nbsp;Bohong Li ,&nbsp;Lingdi Ma","doi":"10.1016/j.pscia.2023.100013","DOIUrl":"10.1016/j.pscia.2023.100013","url":null,"abstract":"<div><p>Matrine is the main component extracted from legumes and has extensive anti-cancer effects; however, its molecular mechanism is unclear. In our study, we found that matrine induced vacuolation in leukemia cells is closely related to cell proliferation inhibition. Vacuolization was reversed after matrine removal. The neutral red staining assay indicated that the matrine-induced vacuoles were acidic, and the vacuoles originated mostly from the lysosome or endosome, as observed by transmission electron microscope (TEM) and fluorescence microscopy localization of LAMP-GFP. Furthermore, single-cell RNA sequencing (RNA-seq) demonstrated that the expression of vacuolation- and lysosomal-related genes were up-regulated after matrine treatment, and western blot (WB) and flow cytometry (FCM) analysis confirmed that matrine inhibits intracellular proteolytic enzyme expression and activity, suggesting that matrine may inhibit lysosomal function. In addition, we identified that matrine significantly up-regulated the expression levels of vacuolar ATPase (V-ATPase) subunits in cells, and the V-ATPase inhibitor effectively reversed the occurrence of cell vacuoles, suggesting that V-ATPase plays an important role in matrine-induced vacuoles. The molecular structure of matrine was further analyzed, and the protonation of matrine in lysosomes to activate V-ATPase may be a direct cause of vacuole formation. Our results revealed a new molecular mechanism by which matrine inhibit leukemia cell proliferation.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000119/pdfft?md5=61fa6d3ffb404559344c3c79741c4503&pid=1-s2.0-S2773216923000119-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progresses in the study of polysaccharide from medicinal plants of the Asclepiadaceae family","authors":"He Xiao ,&nbsp;Ziqing Zeng ,&nbsp;Wenjie Jiang","doi":"10.1016/j.pscia.2024.100045","DOIUrl":"https://doi.org/10.1016/j.pscia.2024.100045","url":null,"abstract":"<div><p>Medicinal plants from the Asclepiadaceae family, such as Luo Mo (<em>Metaplexis japonica</em> Makino), Xu Changqing (<em>Cynanchum paniculatum</em>), and Bai Wei (<em>Cynanchum atratum</em> Bge.), have long been staples in Traditional Chinese Medicine (TCM) due to their wide range of pharmacological activities (Su et al., 2021) [1]. These beneficial properties are largely attributed to compounds like saponins, alkaloids, and polysaccharides. Polysaccharides, in particular, are vital components in TCM and have garnered increasing attention for their diverse therapeutic effects. Polysaccharides from Asclepiadaceae plants are reported to exhibit a variety of pharmacological activities, including anti-radiation, anti-tumor, anti-fatigue, antioxidant, anti-hyperlipidemic, immune-boosting, and liver-protective effects. These polysaccharides have complex structures made up of different monosaccharides, contributing to their wide range of activities. In this review, we provide a comprehensive summary of the isolation, purification, structural characterization, and pharmacological activities of polysaccharides from medicinal plants in the Asclepiadaceae family. We begin by outlining the methods used for the extraction, isolation, and purification of these polysaccharides. Next, we delve into the pharmacological activities of the isolated polysaccharides. Finally, we discuss the potential clinical applications of these polysaccharides in treating various diseases and highlight areas that require further investigation.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000114/pdfft?md5=d3e3439805917f3195d27ad1e679cd87&pid=1-s2.0-S2773216924000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed treatment with hydro-ethanolic extract of Khaya grandifoliola protects mice from acetaminophen-hepatotoxicity through inhibition of c-Jun N-terminal kinase phosphorylation and mitochondrial dysfunction","authors":"Arnaud Fondjo Kouam ,&nbsp;Ibrahim Njingou ,&nbsp;Nina Jeannette Pekam Magoudjou ,&nbsp;Hamed Bechir Ngoumbe ,&nbsp;Philipe Herman Nfombouot Njitoyap ,&nbsp;Elisabeth Menkem Zeuko'o ,&nbsp;Frédéric Nico Njayou ,&nbsp;Paul Fewou Moundipa","doi":"10.1016/j.pscia.2024.100049","DOIUrl":"10.1016/j.pscia.2024.100049","url":null,"abstract":"<div><p>The use of N-acetylcysteine against acetaminophen(APAP)-induced hepatotoxicity, a leading cause of liver injury, has several drawbacks, including short therapeutic windows. <em>Khaya grandifoliola</em> (Meliaceae) has been traditionally used to manage liver-related diseases, and many reports have confirmed its hepatoprotective properties. However, its therapeutic potential as an antidote against APAP-induced hepatotoxicity has yet to be proven in a clinically relevant model. This study aimed to verify the efficacy of delayed treatment with the hydroethanolic extract of <em>K. grandifoliola</em> (KgE) in suppressing the early injury phase of APAP pathophysiology. KgE was analyzed using HPLC/UV. Acute oral toxicity tests were conducted in mice to determine the therapeutic dose of KgE. Mice were treated with 300 ​mg/kg APAP; 1h and 12h later, they were treated with either predetermined doses of KgE or 20 ​mg/kg c-Jun N-Terminal Kinase (JNK) inhibitor SP600125, which served as a reference antidote. At 6h and 24h after APAP treatment, the parameters of liver damage and mitochondrial dysfunction, phosphorylation of JNK, and mitochondrial translocation were assessed. KgE at a dose of 5000 ​mg/kg was safe for mice. Accordingly, 100, 200, and 400 ​mg/kg were selected as curative treatments. Delayed administration of KgE reversed the histopathological changes in the liver, inhibited serum levels of alanine aminotransferase, reduced the liver content of nitric oxide and malondialdehyde, and restored hepatic glutathione pools and superoxide dismutase and catalase activities in APAP-intoxicated mice. Moreover, KgE prevented APAP-induced JNK phosphorylation and p-JNK mitochondrial translocation and rescued the activities of mitochondrial enzyme complexes II and V. HPLC/UV analysis revealed the presence of gallic acid, Quercetin and Silibinin, with retention times of 3.77, 11.63 and 11.95 ​min as the major active ingredients present in KgE. Our findings demonstrate that post-treatment with KgE protects the mouse liver from APAP-hepatotoxicity through the inhibition of JNK activation and mitochondrial dysfunction<strong>.</strong></p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000151/pdfft?md5=5d0d9d2a2dcad48b981b9abb76c4d105&pid=1-s2.0-S2773216924000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of LibidUp-PE supplement on premature ejaculation: A randomized, placebo-controlled double-blind, crossover study","authors":"Jagadeesan M ,&nbsp;Adhisaya A ,&nbsp;T. Srinivasan ,&nbsp;Alphienes Stanley Xavier ,&nbsp;Pavithra Anandan ,&nbsp;Rajappan Chandra Satish Kumar ,&nbsp;Thangavel Mahalingam Vijayakumar","doi":"10.1016/j.pscia.2023.100033","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100033","url":null,"abstract":"<div><p>Premature ejaculation (PE) is the most common male sexual dysfunction. Selective serotonin reuptake inhibitors (SSRIs) are currently recommended for PE. However, the side effects of SSRIs, such as nausea, vomiting, and xerostomia, pose challenges to clinicians. Simultaneously, evidence indicates that psychological and behavioral treatments are often insufficient. LibidUp-PE is a nutraceutical designed to enhance sexual wellness and contains a combination of essential amino acids to boost stamina and vigor, addressing concerns like erectile dysfunction (ED). This study aimed to assess the safety and efficacy of LibidUp-PE in the treatment of PE. In this crossover, double-blind, placebo-controlled trial, 76 patients with PE were randomly divided into two groups. Group A received LibidUp-PE, whereas Group B received a placebo for 12 weeks. Following a 2-week wash-out period, the groups switched treatments for another 12 weeks. Intravaginal ejaculatory latency time (IELT) and post-ejaculatory refractory time (PERT) were measured as the primary outcomes to evaluate PE improvement. Plasma serotonin levels were measured as secondary parameters using enzyme-linked immunosorbent assay. The results showed that LibidUp-PE significantly improved the IELT score, increasing from 0.8 ± 0.2 min to 2.9 ± 1.1 min (<em>p</em> &lt; 0.01). PERT scores also significantly decreased from 15.8 ± 1.7 min to 5.6 ± 0.6 min after 12 weeks of LibidUp-PE treatment. Plasma serotonin levels significant increased from 93.6 ± 7.8 ng/mL to 168.4 ± 12.8 ng/mL (<em>p</em> &lt; 0.001) with LibidUp-PE treatment. In contrast, no significant improvements were observed in the placebo group. Notably, none of the participants withdrew their consent due to adverse reactions, which is indicative of the safety and tolerability of LibidUp-PE. In conclusion, 12-week treatment with LibidUp-PE demonstrated a beneficial effect in reducing PE symptoms, as reflected by improved IELT, reduced PERT, and increased plasma serotonin levels. Therefore, LibidUp-PE could be a promising solution for individuals with PE.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000314/pdfft?md5=3802bdfde5ac6739968ead8e62214a4c&pid=1-s2.0-S2773216923000314-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138738896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sos1 deficiency ameliorates oncogenic KRAS-mediated hematopoietic stem cell exhaustion and myeloid progenitor expansion","authors":"Maoshuo Yang ,&nbsp;Lanlan Liu ,&nbsp;Yaqing Miao ,&nbsp;Yongxin Jia ,&nbsp;Sijia Tian ,&nbsp;Limei Wang ,&nbsp;Fabao Liu ,&nbsp;Xiaona You","doi":"10.1016/j.pscia.2024.100053","DOIUrl":"10.1016/j.pscia.2024.100053","url":null,"abstract":"<div><div>Constitutive <em>KRAS</em> activating mutations are prevalent in hematopoietic malignancies. Our previous study showed that the deficiency of <em>Sos1</em> prolongs the survival of <em>Kras</em>^G12D/+ mice. However, whether <em>Sos1</em> deletion ameliorates oncogenic <em>Kras</em>-mediated hematopoietic defects remains unknown. Here, we found that <em>Sos1</em> deletion restored <em>Kras</em>^G12D-mediated hematopoietic stem cell (HSC) and multipotent progenitor (MPP) exhaustion by maintaining quiescent HSC and MPP pools. <em>Sos1</em> knockout attenuates hyperactivation of ERK signaling in <em>Kras</em>^G12D/+ HSCs and MPPs. Additionally, the loss of <em>Sos1</em> reduced the frequency and colony-forming capability of myeloid progenitors in <em>Kras</em>^G12D/+ mice, resulting in a less severe myeloproliferative neoplasm phenotype. Moreover, <em>Sos1</em> knockout prolonged the survival of <em>Kras</em>^G12D/+ mice in a cell-autonomous manner. In general, cells with <em>Sos1</em> deletion remained sensitive to MEK and JAK inhibition, suggesting that combined Sos1 inhibition and other therapies could be a promising strategy for the treatment of oncogenic <em>KRAS</em>-driven leukemia.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the underlying mechanism of Ziziphi Spinosae Semen for treating anxiety disorder in a zebrafish sleep deprivation model","authors":"Jian Zhang ,&nbsp;Junli Feng ,&nbsp;Chenyu Feng","doi":"10.1016/j.pscia.2023.100019","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100019","url":null,"abstract":"<div><p>Anxiety and depression are the most prevalent psychiatric disorders in the world, and they are highly comorbid with each other. <em>Ziziphi Spinosae Semen</em> (ZSS) is a traditional Chinese herbal medicine widely used in the treatment of insomnia and anxiety in clinical practice. To explore the effects of ZSS in alleviating anxiety in a sleep deprivation (SD) zebrafish model, the locomotor activity performance and anxiety behavior of these experimental fish were evaluated, and the underlying mechanisms of its anti-anxiety effect were examined by analyzing the transcriptomics of brain tissues. Results indicated that ZSS could significantly reduce the freezing duration and alleviate anxiety-like behavior. Moreover, ZSS was effective in promoting melatonin biosynthesis and synaptic transmission, modulating circadian rhythm, and preventing inflammatory response and oxidative stress, as evidenced by the expression alterations of the key anti-oxidation genes (<em>GCLC</em>, <em>GPX1A</em>, <em>GSR</em>, <em>NRF2A</em> and <em>PRDX1</em>) and pro-inflammatory cytokine (<em>IL2RGA</em>, <em>IL6</em> and <em>IL17A/F1</em>). These findings will contribute to the understanding of how ZSS alleviates SD-induced anxiety, and provide a theoretical basis for the clinical application of ZSS.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277321692300017X/pdfft?md5=9f120bcfb614ca105e90736b266f8718&pid=1-s2.0-S277321692300017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92107640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial peptides: A novel and promising arsenal against methicillin-resistant Staphylococcus aureus (MRSA) infections","authors":"Tope T. Odunitan ,&nbsp;Adegboye O. Oyaronbi ,&nbsp;Fakuade A. Adebayo ,&nbsp;Paul A. Adekoyeni ,&nbsp;Boluwatife T. Apanisile ,&nbsp;Tolu D. Oladunni ,&nbsp;Oluwatosin A. Saibu","doi":"10.1016/j.pscia.2023.100034","DOIUrl":"10.1016/j.pscia.2023.100034","url":null,"abstract":"<div><p>Despite years of research, technological advancements, and the widespread use of vaccines and antibiotics as tools to combat microbial threats to humans, methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) infections remain a serious threat to global healthcare systems. The challenge of MRSA is a result of the bacteria's remarkably rapid evolution and adaptation, building up a collection of resistance genes that defeat the mechanism of traditional antibiotics. Conventional antibiotics, including the most notable beta-lactam antibiotics, such as penicillin and cephalosporin, are increasingly inadequate against the rapid adaptability and resistance of MRSA. Consequently, the scientific community's therapeutic arsenal for battling MRSA infections is becoming increasingly limited, necessitating innovative interventions<strong>.</strong> Antimicrobial peptides (AMPs), with their precise targeting mechanisms and innate modifiability, have emerged as promising therapeutic agents. By selectively interrupting bacterial processes and boosting innate immunological responses, AMPs offer a multifaceted strategy. Modern biotechnological and bioinformatics advancements have enabled the refinement of AMPs for improved efficacy. This comprehensive review delves into the intricate facets of MRSA pathogenicity, determinants of resistance, foundational tenets of peptide-based therapeutics, and recent scientific breakthroughs. A comprehensive analysis of the current research landscape, clinical implications, and persistent challenges underscores the potential of precisely tailored peptides as formidable weapons for counteracting the enduring threat of MRSA infections.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216923000326/pdfft?md5=8b1f8fd80d3b9643c6673743091d39bf&pid=1-s2.0-S2773216923000326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139019029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting active RAS with molecular glue","authors":"Wenjing Su ,&nbsp;Xuben Hou","doi":"10.1016/j.pscia.2024.100047","DOIUrl":"10.1016/j.pscia.2024.100047","url":null,"abstract":"<div><p>Activating mutations in RAS genes, notably KRASG12C, are pervasive in numerous cancers, presenting formidable challenges to therapy due to their elusive druggability. The landmark discovery of KRASG12C allosteric inhibitors marked a transformative milestone in cancer treatment, resulting in the approval of sotorasib and adagrasib. However, limitations in the depth and duration of response prompted the quest for alternative strategies. Recently, Holderfield et al., Wasko et al., and Jiang et al. reported on tri-complex inhibitors, namely RMC-7977 and RMC-6236, targeting activated RAS variants, demonstrating promising preclinical efficacy surpassing adagrasib. These advancments signify a paradigm shift in RAS oncology, promising enduring therapeutic benefits and warranting further clinical exploration.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773216924000138/pdfft?md5=acdbb72e8561efb2719e3f80e8eeec17&pid=1-s2.0-S2773216924000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}