Biochimica et biophysica acta. General subjects最新文献

{"title":"Novel regulatory mechanisms of N-glycan sialylation: Implication of integrin and focal adhesion kinase in the regulation","authors":"Tomoya Isaji,&nbsp;Jianguo Gu","doi":"10.1016/j.bbagen.2024.130617","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130617","url":null,"abstract":"<div><h3>Background</h3><p>Sialylation of glycoproteins, including integrins, is crucial in various cancers and diseases such as immune disorders. These modifications significantly impact cellular functions and are associated with cancer progression. Sialylation, catalyzed by specific sialyltransferases (STs), has traditionally been considered to be regulated at the mRNA level.</p></div><div><h3>Scope of review</h3><p>Recent research has expanded our understanding of sialylation, revealing ST activity changes beyond mRNA level variations. This includes insights into COPI vesicle formation and Golgi apparatus maintenance and identifying specific target proteins of STs that are not predictable through recombinant enzyme assays.</p></div><div><h3>Major conclusions</h3><p>This review summarizes that Golgi-associated pathways largely influence the regulation of STs. GOLPH3, GORAB, PI4K, and FAK have become critical elements in sialylation regulation. Some STs have been revealed to possess specificity for specific target proteins, suggesting the presence of additional, enzyme-specific regulatory mechanisms.</p></div><div><h3>General significance</h3><p>This study enhances our understanding of the molecular interplay in sialylation regulation, mainly focusing on the role of integrin and FAK. It proposes a bidirectional system where sialylations might influence integrins and vice versa. The diversity of STs and their specific linkages offer new perspectives in cancer research, potentially broadening our understanding of cellular mechanisms and opening avenues for new therapeutic approaches in targeting sialylation pathways.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobleaching FRET-FLIM-ICS for quaternary structure quantification on cells. Theory and simulations","authors":"Andrew H.A. Clayton","doi":"10.1016/j.bbagen.2024.130618","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130618","url":null,"abstract":"<div><p>The oligomerization of proteins is an important biological control mechanism and has several functions in activity and stability of enzymes, structural proteins, ion channels and transcription factors. The determination of the relevant oligomeric states in terms of geometry (spatial extent), oligomer size (monomer or dimer or oligomer) and affinity (amounts of monomer, dimer and oligomer) is a challenging biophysical problem. Förster resonance energy transfer and fluorescence fluctuation spectroscopy are powerful tools that are sensitive to proximity and oligomerization respectively. Here it is proposed to combine image-based lifetime-detected Forster resonance energy transfer with image correlation spectroscopy and photobleaching to determine distances, oligomer sizes and oligomer distributions. Simulations for simple oligomeric forms illustrate the potential to improve the discrimination between different quaternary states in the cellular milieu.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304416524000618/pdfft?md5=8fbcf605ea313027e5199a2d59149951&pid=1-s2.0-S0304416524000618-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of HEK293A cells with a CRISPR/Cas9-mediated TDP1 knockout","authors":"Nadezhda S. Dyrkheeva ,&nbsp;Alexandra L. Zakharenko ,&nbsp;Anastasia A. Malakhova ,&nbsp;Larisa S. Okorokova ,&nbsp;Dmitry N. Shtokalo ,&nbsp;Sergey P. Medvedev ,&nbsp;Alexey A. Tupikin ,&nbsp;Marsel R. Kabilov ,&nbsp;Olga I. Lavrik","doi":"10.1016/j.bbagen.2024.130616","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130616","url":null,"abstract":"<div><p>Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on structural similarity. TDP1 is a key enzyme of the repair of stalled topoisomerase 1 (TOP1)–DNA complexes. Previously, with the CRISPR/Cas9 method, we obtained HEK293A cells with a homozygous knockout of the <em>TDP1</em> gene and used the <em>TDP1</em> knockout cells as a cellular model for studying mechanisms of action of an anticancer therapy. In the present work, we hypothesized that the TDP1 knockout would alter the expression of DNA repair–related genes. By transcriptomic analysis, we investigated for the first time the effect of the <em>TDP1</em> gene knockout on genes' expression changes in the human HEK293A cell line. We obtained original data implying a role of TDP1 in other processes besides the repair of the DNA–TOP1 complex. Differentially expressed gene analysis revealed that TDP1 may participate in cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, a cytokine response, and the MAPK signaling pathway.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Distinctive domains and activity regulation of core fucosylation enzyme FUT8” [BBA General Subjects 1868 (2024)/130561]","authors":"Seita Tomida ,&nbsp;Masamichi Nagae ,&nbsp;Yasuhiko Kizuka","doi":"10.1016/j.bbagen.2024.130615","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130615","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304416524000588/pdfft?md5=ae5cfe1c9ad3447ce0b955766d7dca0d&pid=1-s2.0-S0304416524000588-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAMSAP3-mediated regulation of HMGB1 acetylation and subcellular localization in lung cancer cells: Implications for cell death modulation","authors":"Natsaranyatron Singharajkomron ,&nbsp;Suthasinee Seephan ,&nbsp;Iksen Iksen ,&nbsp;Naphat Chantaravisoot ,&nbsp;Piriya Wongkongkathep ,&nbsp;Yoshihiro Hayakawa ,&nbsp;Varisa Pongrakhananon","doi":"10.1016/j.bbagen.2024.130614","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130614","url":null,"abstract":"<div><h3>Background</h3><p>Deregulation of cell death is a common characteristic of cancer, and resistance to this process often occurs in lung cancer. Understanding the molecular mechanisms underlying an aberrant cell death is important. Recent studies have emphasized the involvement of calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) in lung cancer aggressiveness, its influence on cell death regulation remains largely unexplored.</p></div><div><h3>Methods</h3><p><em>CAMSAP3</em> was knockout in lung cancer cells using CRISPR-Cas9 system. Cell death and autophagy were evaluated using MTT and autophagic detection assays. Protein interactions were performed by proteomic analysis and immunoprecipitation. Protein expressions and their cytoplasmic localization were analyzed through immunoblotting and immunofluorescence techniques.</p></div><div><h3>Results</h3><p>This study reveals a significant correlation between low <em>CAMSAP3</em> expression and poor overall survival rates in lung cancer patients. Proteomic analysis identified high mobility group box 1 (HMGB1) as a candidate interacting protein involved in the regulation of cell death. Treatment with trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs) resulted in increased HMGB1 acetylation and its translocation to the cytoplasm and secretion, thereby inducing autophagic cell death. However, this process was diminished in CAMSAP3 knockout lung cancer cells. Mechanistically, immunoprecipitation indicated an interaction between CAMSAP3 and HMGB1, particularly with its acetylated form, in which this complex was elevated in the presence of TSA.</p></div><div><h3>Conclusions</h3><p>CAMSAP3 is prerequisite for TSA-mediated autophagic cell death by interacting with cytoplasmic acetylated HMGB1 and enhancing its release.</p></div><div><h3>Significant</h3><p>This finding provides molecular insights into the role of CAMSAP3 in regulating cell death, highlighting its potential as a therapeutic target for lung cancer treatment.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140539160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics of structural effects of reactive carbonyl species derivate of lipid peroxidation on bovine serum albumin","authors":"Rafael Pineda-Alemán ,&nbsp;Camila Cabarcas-Herrera ,&nbsp;Antistio Alviz-Amador ,&nbsp;Rodrigo Galindo-Murillo ,&nbsp;Humberto Pérez-Gonzalez ,&nbsp;Erika Rodríguez-Cavallo ,&nbsp;Darío Méndez-Cuadro","doi":"10.1016/j.bbagen.2024.130613","DOIUrl":"https://doi.org/10.1016/j.bbagen.2024.130613","url":null,"abstract":"<div><h3>Background</h3><p>Serum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases.</p></div><div><h3>Methods</h3><p>To elucidate structural effects of protein carbonylation with RCSs on BSA, parameters for six new non-standard amino acids were designated and molecular dynamics simulations of its mono‑carbonylated-BSA systems were conducted in the AMBER force field. Trajectories were evaluated by RMSD, RMSF, PCA, RoG and SASA analysis.</p></div><div><h3>Results</h3><p>An increase in the conformational instability for all proteins modified with local changes were observed, without significant changes on the BSA global three-dimensional folding. A more relaxed compaction level and major solvent accessible surface area for modified systems was found. Four regions of high molecular fluctuation were identified in all modified systems, being the subdomains IA and IIIB those with the most remarkable local conformational changes. Regarding essential modes of domain movements, it was evidenced that the most representatives were those related to IA subdomain, while IIIB subdomain presented discrete changes.</p></div><div><h3>Conclusions</h3><p>RCSs induces local structural changes on mono‑carbonylated BSA. Also, this study extends our knowledge on how carbonylation by RCSs induce structural effects on proteins.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304416524000564/pdfft?md5=8179fe45ce62f7c3aecf9737b97cb60e&pid=1-s2.0-S0304416524000564-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140542868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three species multiplexing of fluorescent dyes and gold nanoclusters recovered with fluorescence lifetime correlation spectroscopy","authors":"Malavika Kayyil Veedu ,&nbsp;Agata Hajda ,&nbsp;Joanna Olesiak-Bańska ,&nbsp;Jérôme Wenger","doi":"10.1016/j.bbagen.2024.130611","DOIUrl":"10.1016/j.bbagen.2024.130611","url":null,"abstract":"<div><p>Biosensor applications often require the simultaneous detection of multiple analytes, with a clear need to go beyond the traditional multiplexing relying on distinct fluorescent dyes across the visible spectrum. Fluorescence lifetime correlation spectroscopy (FLCS) is a powerful approach taking advantage of the fluorescence lifetime information to separate the contributions of different fluorescent species with overlapping emission spectra. However, so far FLCS detection has been demonstrated only on binary mixtures of two fluorescent dyes, limiting its multiplexing capabilities. Here, we report the first quantitative FLCS measurements within a ternary mixture composed of three different fluorescent emitters with near-identical emission spectra. Two organic fluorescent dyes, Alexa Fluor 647 and CF640R, are combined with water-soluble Au₁₈(SG)₁₄ gold nanoclusters. Our experimental data establish that FLCS allows to accurately determine individual concentrations within intricate ternary mixtures. Another major aspect of interest concerns the assessment of the suitability of gold nanoclusters for FLCS multiplexing applications. With their microsecond lifetime and stable emission characteristics, gold nanoclusters add a valuable new aspect to the array of FLCS probes. Extending FLCS multiplexing beyond binary mixtures paves the way for further progress in the simultaneous highly parallel biosensing of multiple species.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304416524000540/pdfft?md5=1c62b57743a45715aa07ecb6427c3af9&pid=1-s2.0-S0304416524000540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyamine release and vesicular polyamine transporter expression in megakaryoblastic cells and platelets","authors":"Mizuki Uehara,&nbsp;Ayaka Fukumoto,&nbsp;Hiroshi Omote,&nbsp;Miki Hiasa","doi":"10.1016/j.bbagen.2024.130610","DOIUrl":"10.1016/j.bbagen.2024.130610","url":null,"abstract":"<div><p>Polyamines not only play essential roles in cell growth and function of living organisms but are also released into the extracellular space and function as regulators of chemical transduction, although the cells from which they are released and their mode of release are not well understood. The vesicular polyamine transporter (VPAT), encoded by the <em>SLC18B1</em> is responsible for the vesicular storage of spermine and spermidine, followed by their vesicular release from secretory cells. Focusing on VPAT will help identify polyamine-secreting cells and new polyamine functions. In this study, we investigated the possible involvement of VPAT in vesicular release of polyamines in MEG-01 clonal megakaryoblastic cells and platelets. RT-PCR, western blotting, and immunohistochemistry revealed VPAT expression in MEG-01 cells. MEG-01 cells secreted polyamines upon A23187 stimulation in the presence of Ca²⁺, which is temperature-dependent and sensitive to bafilomycin A₁. A23187-induced polyamine secretion from MEG-01 cells was reduced by treatment with reserpine, VPAT inhibitors, or VPAT RNA interference. Platelets also expressed VPAT, displaying a punctate distribution, and released spermidine upon A23187 and thrombin stimulation. These findings have demonstrated VPAT-mediated vesicular polyamine release from MEG-01 cells, suggesting the presence of similar vesicular polyamine release mechanisms in platelets.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing subcellular protein localization mapping analysis using Sc2promap utilizing attention mechanisms","authors":"Kaitai Han,&nbsp;Xi Liu,&nbsp;Guocheng Sun,&nbsp;Zijun Wang,&nbsp;Chaojing Shi,&nbsp;Wu Liu,&nbsp;Mengyuan Huang,&nbsp;Shitou Liu,&nbsp;Qianjin Guo","doi":"10.1016/j.bbagen.2024.130601","DOIUrl":"10.1016/j.bbagen.2024.130601","url":null,"abstract":"<div><h3>Background</h3><p>Aberrant protein localization is a prominent feature in many human diseases and can have detrimental effects on the function of specific tissues and organs. High-throughput technologies, which continue to advance with iterations of automated equipment and the development of bioinformatics, enable the acquisition of large-scale data that are more pattern-rich, allowing for the use of a wider range of methods to extract useful patterns and knowledge from them.</p></div><div><h3>Methods</h3><p>The proposed sc2promap (Spatial and Channel for SubCellular Protein Localization Mapping) model, designed to proficiently extract meaningful features from a vast repository of single-channel grayscale protein images for the purposes of protein localization analysis and clustering. Sc2promap incorporates a prediction head component enriched with supplementary protein annotations, along with the integration of a spatial-channel attention mechanism within the encoder to enables the generation of high-resolution protein localization maps that encapsulate the fundamental characteristics of cells, including elemental cellular localizations such as nuclear and non-nuclear domains.</p></div><div><h3>Results</h3><p>Qualitative and quantitative comparisons were conducted across internal and external clustering evaluation metrics, as well as various facets of the clustering results. The study also explored different components of the model. The research outcomes conclusively indicate that, in comparison to previous methods, Sc2promap exhibits superior performance.</p></div><div><h3>Conclusions</h3><p>The amalgamation of the attention mechanism and prediction head components has led the model to excel in protein localization clustering and analysis tasks.</p></div><div><h3>General significance</h3><p>The model effectively enhances the capability to extract features and knowledge from protein fluorescence images.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies","authors":"Hazem Elkady ,&nbsp;Hazem A. Mahdy ,&nbsp;Mohammed S. Taghour ,&nbsp;Mohammed A. Dahab ,&nbsp;Alaa Elwan ,&nbsp;Mohamed Hagras ,&nbsp;Mona H. Hussein ,&nbsp;Ibrahim M. Ibrahim ,&nbsp;Dalal Z. Husein ,&nbsp;Eslam B. Elkaeed ,&nbsp;Aisha A. Alsfouk ,&nbsp;Ahmed M. Metwaly ,&nbsp;Ibrahim H. Eissa","doi":"10.1016/j.bbagen.2024.130599","DOIUrl":"10.1016/j.bbagen.2024.130599","url":null,"abstract":"<div><h3>Background</h3><p>VEGFR-2 has emerged as a prominent positive regulator of cancer progression.</p></div><div><h3>Aim</h3><p>Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2.</p></div><div><h3>Methods</h3><p>Design and synthesis of new thiazolidine-2,4-diones followed by extensive <em>in vitro</em> studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. <em>In silico</em> investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed.</p></div><div><h3>Results</h3><p>Compound <strong>15</strong> showed the strongest VEGFR-2 inhibitory activity with an IC₅₀ value of 0.066 μM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC₅₀ values ranging from 0.04 to 4.71 μM, relative to sorafenib (IC₅₀ = 2.24 ± 0.06 and 3.17 ± 0.01 μM against HepG2 and MCF-7, respectively). Also, compound <strong>15</strong> showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound <strong>15</strong> showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound <strong>15</strong> had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound <strong>15</strong> in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound <strong>15</strong> to interact with VEGFR-2.</p></div><div><h3>Conclusion</h3><p>Compound <strong>15</strong> has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}