Letters in Drug Design & Discovery最新文献

{"title":"Clinical Efficacy of Vaccaria Segetalis Seeds and Gleditsia Sinensis Lam\u0000Thorns on Prostate Cancer: A Preliminary Mechanism Analysis Based on\u0000Network Pharmacology","authors":"Cheng-Yu Wu, Hsiu-Hsien Huang, Qiao Li, Lei Zhang","doi":"10.2174/1570180820666230502152114","DOIUrl":"https://doi.org/10.2174/1570180820666230502152114","url":null,"abstract":"\u0000\u0000The mechanism of Vaccaria segetalis (VS) seeds and Gleditsia sinensis Lam (GS)\u0000thorns in the treatment of prostate cancer (PC) was analyzed via network pharmacological analysis\u0000methods and molecular docking.\u0000\u0000\u0000\u0000The Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP) was\u0000used to screen the PC’s effective components and targets; GeneCards and OMIM databases to search for\u0000targets related to PC. The intersection target was uploaded to the STRING database to obtain a proteinprotein\u0000interaction (PPI) network; and the key targets were screened from the PPI network via R language,\u0000CytoNCA, and CytoHubba tools. Gene Ontology (GO) and Kyoto encyclopedia of genes and genome\u0000(KEGG) pathway enrichment tools were used to analyze biological processes and molecular docking\u0000of key targets via AutoDock Vina software.\u0000\u0000\u0000\u0000A total of 13 compounds, 229 nodes, 879 edges, and 20 key targets were obtained through the\u0000PPI network. Go and KEGG analysis showed that the intersection targets of VS and GS with PC were\u0000mainly involved in regulating cell promotion, cell apoptosis, cell cycle, and reversing epithelialmesenchymal\u0000transition (EMT) processing. Molecular docking revealed that the relevant targets of potential\u0000PC were characterized with stabilized affinity. Specifically, the targets with better affinity included\u0000estrogen receptor 1 (ESR1) with kaempferol, transcription factor p65 (RELA) with fisetin, kaempferol,\u0000quercetin, and mitogen-activated protein kinase 1 (MAPK1) with fisetin, and G1/S-specific cyclin-D1\u0000(CCND1) with fisetin, kaempferol, and quercetin.\u0000\u0000\u0000\u0000In summary, this study reveals potential molecular therapeutic mechanisms of VS and GS in\u0000PC and provides a reference for the wide application of VS and GS in the clinical management of PC.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"54 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91471448","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":"Coronavirus Inhibitory Activity of Tamarind Indica","authors":"K. Danao, Ruchi Shivhare, Deweshri Nandurkar, Vijayshri Rokde, U. Mahajan","doi":"10.2174/1570180820666230428110803","DOIUrl":"https://doi.org/10.2174/1570180820666230428110803","url":null,"abstract":"\u0000\u0000SARS-COVID-19 is an infectious disease, the causative agent Caroni virus. WHO announced the pandemic on 3rd November 2020 to the whole world.\u0000\u0000\u0000\u0000Severe Acute Respiratory Syndrome COVID-19 is an infectious disease globally declared a pandemic by WHO. There is a need to find the proper medication for recovery. The study uses the molecular docking method to predict the anti-covid activity of plant phytoconstituents of Tamarind indica.\u0000\u0000\u0000\u0000Molecular docking techniques were accomplished to search the binding pattern of plant phytoconstituents of T. indica against the crystal structure SARS-CoV-2 enzyme (PDB ID: 6LU7) with the help of PyRx virtual screening software to study the amino acid interaction and inhibitory potential of phytoconstituents of T. indica. In addition, we performed a pharmacokinetic and toxicological study of plant phytoconstituents of T. indica using SwissADME and the pkCSM online server.\u0000\u0000\u0000\u0000The phytoconstituents of Plant T. indica docking results proposed that apigenin (-7.8 kcal/mol), epicatechin (-7.1 kcal/mol) and taxifolin (-7.5 kcal/mol) show the best binding energy as compared to favipiravir (-5.2 kcal/mol). The phytoconstituents exposed promising interaction with amino acid residue, leading to an inhibitory effect against the SARS-CoV-2 enzyme (PDB ID: 6LU7). Further, ADMET studies showed that pharmacokinetics and toxicological parameters are within acceptable limits.\u0000\u0000\u0000\u0000In silico study revealed that the phytochemicals of T.indica show promising inhibitory results against the SARS-CoV-2 enzyme (PDB ID: 6LU7). Moreover, the traditional benefits of T.indica were clinical treatment and drug discovery.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"226 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78479479","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":"Mesalamine may be a plausible therapeutic agent for the management of diabetic wounds: A computational approach","authors":"Vidyasrilekha. Yele, Bharat Kumar Reddy Sanapalli, Jayrajsinh Jadeja, Priya. Kakasaniya, Jaydip. Asodariya","doi":"10.2174/1570180820666230427145116","DOIUrl":"https://doi.org/10.2174/1570180820666230427145116","url":null,"abstract":"\u0000\u0000Validation of mesalamine (MS) as a potential therapeutic agent in treating diabetic wound (DW) healing using in silico approach.\u0000\u0000\u0000\u0000Diabetic wound (DW) is a serious consequence of diabetes that frequently results in the amputation of the affected organ. Maggot therapy, pressure off-loading, surgical intervention, glucose control, hyperbaric oxygen therapy, wound debridement, and other treatments are currently available for DW. However, the majority of people do not meet all DW requirements due to significant pathology and the high expense of the solutions.\u0000\u0000\u0000\u0000To address the issues with current conventional therapy, we reasoned that repurposing existing medication (MS) to a target receptor that plays a significant role in the progression of DW might be advantageous. Mesalamine (MS), also known as Mesalazine or 5- Aminosalicylic acid, is an aminosalicylate anti-inflammatory used to treat inflammatory bowel disease (IBD), ulcerative colitis (UC), inflamed anus or rectum. The complicated pathophysiology of DW, which includes prolonged inflammation, increased infection, decreased cell proliferation, and migration, is a serious issue. As a result, we chose the MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors as a universal target for treating the complex pathogenesis of DW. The use of MS as a therapeutic modulator on MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors was studied in the current hypothetical investigation.\u0000\u0000\u0000\u0000Computational studies such as molecular docking and MMGBSA were performed by using the Schrödinger suite.\u0000\u0000\u0000\u0000Computational investigations, such as molecular docking and MMGBSA were used to test our theory. It is clear from the in silico methods that MS has a higher binding affinity for the designated receptors. Hence, it is predicted that MS may be a good therapeutic agent to use in the treatment of DW.\u0000\u0000\u0000\u0000As a result of our findings, MS appears to be a unique therapeutic drug for the treatment of DW. However, further studies are highly required to take MS into clinical use.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79193263","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":"Neuroprotective potential of polydatin in combating Parkinson’s disease through the inhibition of Monoamine Oxidase-B and Catechol-o-Methyl Transferase","authors":"Anupom Borah, B. C. Phukan, Rubina Roy, S. Choudhury, P. Bhattacharya","doi":"10.2174/1570180820666230427092537","DOIUrl":"https://doi.org/10.2174/1570180820666230427092537","url":null,"abstract":"\u0000\u0000This study aims to deduce the plausible contribution of polydatin in dopamine replenishment and dopaminergic neuroprotection to unveil its potential as a drug candidate for PD.\u0000\u0000\u0000\u0000Available therapies for the management of dopaminergic degradation in Parkinson’s disease (PD) provide only symptomatic relief and are associated with various adverse effects. Levodopa (L-DOPA) is an age-old therapy in the treatment paradigm of PD, either used as mono-therapy or in combination with the inhibitors of the dopamine catabolising enzymes monoamine oxidase-B (MAO-B) and catechol O-methyltransferase (COMT) for replenishing the levels of the neurotransmitter. The discovery of plant-based novel drug therapies would help to target multiple pathways underlying the disease pathogenesis and are associated with minimal side effects. Polydatin, the precursor of resveratrol, has been explored recently to possess neuroprotective efficacy, however, the molecular mechanisms that underlie the Parkinsonism-associated neurobehavioral recovery as well as the neurorescue potential of polydatin has not been illustrated yet.\u0000\u0000\u0000\u0000The present study aimed to unveil the role of polydatin in dopamine upregulation in PD, by determining its dual inhibitory potential on the enzymes responsible for its breakdown, MAO-B and COMT. The study further aimed to elucidate the role of this molecule in regulating the enzymatic activity of Cytosolic Phospholipase A2 (cPLA2), the crucial enzyme underlying several pathogenic pathways leading to neurodegeneration.\u0000\u0000\u0000\u0000Molecular docking simulation of polydatin with the dopamine catabolizing enzymes MAO-B and COMT, as well as cPLA2, along with their respective known inhibitors was performed using the Molegro Virtual Docker (MVD) 2.1 package.\u0000\u0000\u0000\u0000In-silico analyses revealed that polydatin could significantly inhibit the activities of this dopamine catabolizing enzyme, MAO-B, and COMT with comparable docking scores and more numbers of hydrogen bonds, and weaker interactions as that of their respective available synthetic inhibitors. Moreover, it was found that polydatin could regulate the activity of cPLA2 comparable to its known inhibitors.\u0000\u0000\u0000\u0000Polydatin exhibited efficacy as a potent dopamine replenishing agent by inhibiting its metabolizing enzymes as well as found to have efficacy against neuroinflammation, thereby highlighting the significance of designing novel phyto drugs for combating dopamine deficiency in PD.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79745144","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":"Insight into Quantum Computing and Deep Learning Approach for Drug Design","authors":"D. Paliwal, G. K. Rao, Devdhar Yadav, Prince Raj","doi":"10.2174/1570180820666230427151812","DOIUrl":"https://doi.org/10.2174/1570180820666230427151812","url":null,"abstract":"\u0000\u0000In recent years, substantial modelling breakthroughs have been achieved in artificial intelligence due to new algorithms, improved computer power, and expanded storage capacity. These factors\u0000have made it possible to process large amounts of data in a short amount of time. By using quantum computing in conjunction with deep learning models, it has been possible to explain the characteristics of\u0000ligands and their interactions with biological targets. This contributes to the process of ligand identification and ultimately results in the optimization of drug design. This review explains the extensive use of\u0000quantum deep learning in the development of drug design from traditional to quantum-powered deep\u0000learning neural networks that cover some domains like variational quantum Eigen solver, variational\u0000quantum circuits, quantum convolutional deep neural networks, QC-based deep neural networks for\u0000QSAR, as well as quantized generative models for the discovery of small drug molecules. Quantum computing can execute incredible computational work tenfold faster than current technology, transforming\u0000drug design, development, and post-marketing surveillance. This will reduce the time and resources needed to develop a medicine. Scientific research is moving toward quantum computing since it is anticipated\u0000that QC-based deep learning technologies can predict and mimic the characteristics, structures, and activities of molecules more efficiently than different ML techniques or conventional computers.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"141 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72887523","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":"Neuroprotective and Nootropic Evaluation of Some Important Medicinal Plants in Dementia: A Review","authors":"Songmee Kim, F. Shah, Y. S. Eom, Kyeong Ho Lim","doi":"10.2174/1570180820666230427123641","DOIUrl":"https://doi.org/10.2174/1570180820666230427123641","url":null,"abstract":"\u0000\u0000Dementia is a devitalising decline in neurological acuity, which burdens both high- and low-income countries due to poor diagnostic systems and high healthcare costs. A growing population and rises in deleterious environmental and genetic anomalies aggravate new and aggressive cases of dementia and neurodegenerative disorders. The unparalleled capability of medicinal plants is constantly explored in treating neurological disorders, and some of these phytocompounds are used for treating diseases. However, some of these metabolites are neurotoxic and disrupt DNA polymerase functions. They possess life-threatening side effects and are unable to prevent disease progression. Therefore, it is important to focus on discovering novel compounds from new medicinal plants. Our review encompasses some medicinal plant metabolites recently explored in treating this disease. We also summarized the molecular mechanism of action as determined in in-vitro: the toxic dose, nootropic and neuroprotective effects on neurophysiology and neurotransmitter levels, and the antioxidant effects.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79191534","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":"Discovery of Novel Lysine Methyltransferase (SMYD3) Inhibitors by Utilizing 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation","authors":"YuanZe Shi, M. Shu, XiaoDie Chen, Jiali Li, Na Yu, Jinping Wu, Xuemin Zhao, Zhihua Lin","doi":"10.2174/1570180820666230419082516","DOIUrl":"https://doi.org/10.2174/1570180820666230419082516","url":null,"abstract":"\u0000\u0000To investigate novel isoxazole amide SMYD3 inhibitors as adjuvant anticancer agents for multiple cancers.\u0000\u0000\u0000\u0000SET and MYND Domain-Containing Protein 3 is a hopeful therapeutic target for breast, liver, colon, and prostate cancer.\u0000\u0000\u0000\u0000Novel SMYD3 inhibitors were predicted by the 3D-QSAR models.\u0000\u0000\u0000\u0000In this present work, 3D-QSAR, molecular docking and molecular dynamics (MD) simulations were performed on a series of isoxazole amides-based SMYD3 inhibitors.\u0000\u0000\u0000\u0000Molecular docking revealed residues important to protein-compound interactions, indicating that SMYD3 inhibitors have a strong affinity with and bind to key protein residues such as TYR239, MET190, LYS297 and VAL368. The molecular docking results were further validated by molecular dynamics simulations.\u0000\u0000\u0000\u0000The above information provided significant guidance for the design of novel SMYD3 inhibitors.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79764790","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":"Discovery of Multi-Functional Lead Compounds Originating from Traditional Chinese Medicine for Developing Anti-Depressive Agents via Virtual Screening","authors":"Chu Zhaoxing, Mo Jiajia, Xu Qinlong, Liao JiaMing, Ma Xiaodong, Zhu Qihua, He Guangwei","doi":"10.2174/1570180820666230418104418","DOIUrl":"https://doi.org/10.2174/1570180820666230418104418","url":null,"abstract":"\u0000\u0000The increasing prevalence of depression has become a global health issue. Currently approved anti-depressive including 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), triple reuptake inhibitors (TRIs) and glutamate N-methyl-D-aspartate (NMDA) receptor antagonists have limited effects because of their insufficient efficacy and/or slow onset of action. Developing multifunctional antidepressants that can modulate 5-HT, DA, NE, and NMDA simultaneously can potentially overcome the current drug defects.\u0000\u0000\u0000\u0000This study aimed to explore leads for the development of multi-functional anti-depressive agents that simultaneous triple reuptake inhibitory and NMDA-GluN2B receptor antagonistic activities\u0000\u0000\u0000\u0000This study aimed to explore leads for the development of multi-functional anti-depressive agents that simultaneous triple reuptake inhibitory and NMDA-GluN2B receptor antagonistic activities.\u0000\u0000\u0000\u0000Potential leads were screened virtually from the TCMSP database based on the 3D-Pharmacophore model of TRIs followed by the molecular docking into NMDA-GluN2B receptor, BBB score, and the in-silico toxicity evaluation. The biological activities of discovered leads on 5-HT, NE, and DA reuptake and their effect on the NMDA-GluN2B receptor were evaluated via radio-labeled neurotransmitters and competition radio-ligand binding experiment with [3H] ifenprodil, respectively. Lastly, the antidepressant effect of these potential leads was determined in vivo through the forced swim test in mice\u0000\u0000\u0000\u0000Two compounds were attained as potential leads after the aforementioned experiments. Further in vitro biological evaluation identified Hit-2 as a promising lead that exerted favorable triple 5-HT/DA/NE reuptake inhibitory activity (66.98% inhibition rate at 10μM against hNET, 73.01% inhibition rate at 1μM against hDAT and 86.27% inhibition rate at 1μM against hSERT), as well as potent NMDA-GluN2B receptor antagonistic activity (Ki=115.73±3.54nM). The antidepressant activity of Hit-2 was confirmed through in vivo experiments\u0000\u0000\u0000\u0000Hit-2 not only simultaneously inhibited the reuptake of 5-HT, DA, and NE, and acted as an NMDA-GluN2B receptor antagonist in vitro but also showed in vivo antidepressant activity. These findings may serve as a structural basis for the further development of multi-functional anti-depressive agents.\u0000\u0000\u0000\u0000none\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85070182","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":"QSAR Studies on a Series of Pyrazole Azabicyclo [3.2.1] Octane Sulfonamides N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibitors","authors":"Huan Wang, Shengnan Ren, Liyang Sun, H. Si, Zhuang Yu","doi":"10.2174/1570180820666230418093238","DOIUrl":"https://doi.org/10.2174/1570180820666230418093238","url":null,"abstract":"\u0000\u0000Inflammation is a common and intractable disease for humans. Current anti-inflammatory drugs have a lot of side effects, which cause irreversible damage to the body.\u0000\u0000\u0000\u0000We predict the activity of the N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitor to find more effective compounds.\u0000\u0000\u0000\u0000we established a quantitative structure-activity relationship (QSAR) model by gene expression programming to predict the IC50 values of natural compounds. The NAAA inhibitor, as a cysteine enzyme, plays an important role in the therapy of pain, anti-inflammatory effects and application of other diseases. A total of 36 NAAA inhibitors were optimized by the heuristic method in the CODESSA program to build a linear model. The 27 compounds and 9 compounds were in train and test sets. On this basis, we selected three descriptors and used them to build nonlinear models in gene expression programming.\u0000\u0000\u0000\u0000The best model in the gene expression programming method was found, the square of correlation coefficients of R2 and mean square error for the training set were 0.79 and 0.14, testing set was 0.78 and 0.20, respectively.\u0000\u0000\u0000\u0000From this method, the activity of molecules could be predicted, and the best method was found. Therefore, this model has a stronger predictive ability to develop NAAA inhibitors.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82366025","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":"Ezetimibe inhibits cell viability and invasion by suppressing PI3K/AKT signaling pathway in human osteosarcoma cells","authors":"Qiuyan Weng, Jianning Luo, Yong Zhang, Tongzhou Hu","doi":"10.2174/1570180820666230418113909","DOIUrl":"https://doi.org/10.2174/1570180820666230418113909","url":null,"abstract":"\u0000\u0000Osteosarcoma is one of the most prevalent malignant bone tumors with a poor overall prognosis and mainly happens in children and adolescents. Current therapy strategies still possess a lot of limitations, and new and efficient strategies are required. Ezetimibe was previously reported to have its anti-tumor effect in various tumors, but the investigation of Ezetimibe on osteosarcoma is still limited.\u0000\u0000\u0000\u0000This study explores whether ezetimibe could exert an anti-tumor effect on human osteosarcoma cell lines, U2OS, and Saos-2.\u0000\u0000\u0000\u0000The effect of ezetimibe on the proliferation of osteosarcoma was explored by CCK-8 and colony formation assay. The role of ezetimibe on osteosarcoma cell migration and invasion was explored by wound healing assay and transwell assay. The role of ezetimibe on osteosarcoma cell apoptosis was explored by PI/Annexin V analysis. In addition, a western blot was performed to verify the phenotype.\u0000\u0000\u0000\u0000The flow cytometry assay indicated that ezetimibe could promote osteosarcoma apoptosis. Western blot assay further demonstrated the effect of ezetimibe on proliferation, migration, invasion and apoptosis-related proteins. Finally, the deep anti-tumor effect of ezetimibe contributed to suppressing the PI3K/AKT signaling pathway.\u0000\u0000\u0000\u0000Present data indicated that ezetimibe has an antitumor effect on osteosarcoma and could be considered a future osteosarcoma treatment.\u0000","PeriodicalId":18063,"journal":{"name":"Letters in Drug Design & Discovery","volume":"350 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79861824","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}