Biomolecules & Therapeutics最新文献

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Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4 Pathway via the p300-p53 Axis. 青蒿琥酯通过p300-p53轴调控SLC7A11-GPX4通路抑制皮肤鳞状细胞癌的增殖和迁移
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-24 DOI: 10.4062/biomolther.2024.156
Xinyan Huang, Wenxi Wang, Songzhao Zhang, Lili Li, Jihui Huang
{"title":"Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4 Pathway via the p300-p53 Axis.","authors":"Xinyan Huang, Wenxi Wang, Songzhao Zhang, Lili Li, Jihui Huang","doi":"10.4062/biomolther.2024.156","DOIUrl":"10.4062/biomolther.2024.156","url":null,"abstract":"<p><p>The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC<sub>50</sub> value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured <i>in vitro</i>, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed. The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe<sup>2+</sup> levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth <i>in vivo</i>. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"365-377"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resveratrol from Peanut Sprout Extract Promotes NK Cell Activation and Antitumor Activity. 花生芽提取物中的白藜芦醇促进NK细胞活化和抗肿瘤活性。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.4062/biomolther.2024.133
Hyunmin Chung, Seong Ho Bak, Eunju Shin, Taeho Park, Jinwoo Kim, Hanseul Jeong, Haiyoung Jung, Suk Ran Yoon, Ji-Yoon Noh
{"title":"Resveratrol from Peanut Sprout Extract Promotes NK Cell Activation and Antitumor Activity.","authors":"Hyunmin Chung, Seong Ho Bak, Eunju Shin, Taeho Park, Jinwoo Kim, Hanseul Jeong, Haiyoung Jung, Suk Ran Yoon, Ji-Yoon Noh","doi":"10.4062/biomolther.2024.133","DOIUrl":"10.4062/biomolther.2024.133","url":null,"abstract":"<p><p>Natural killer (NK) cells are innate immune cells that are crucial for anticancer activity and have been developed as an immune cell therapy for leukemia. However, their limited effectiveness against solid tumors has prompted research into methods to enhance NK cell activity through combination therapies. Health supplements capable of boosting immune surveillance against tumor cells are gaining attention owing to their potential benefits. Resveratrol, a stilbenoid produced by several plants including peanuts and grapes, reportedly exerts anticancer effects and can activate immune cells. The peanut sprout extract cultivated with fermented sawdust medium (PSEFS) is rich in resveratrol, leveraging its health benefits in terms of the dry weight of herbal products, thus maximizing the utilization of resveratrol's beneficial properties. Our study compared the efficacy of resveratrol and PSEFS and revealed that PSEFS significantly enhanced NK cell activation compared with an equivalent dose of resveratrol. We investigated the ability of PSEFS to potentiate NK cell anticancer activity, focusing on NK cell survival, tumor cell lysis, and NK cell activation in PSEFS-administered mice. Our findings suggest that PSEFS could be a potential NK cell booster for cancer immunotherapy.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"355-364"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Piperine Regulates Melanogenesis through ERK Activation and Proteasomal Degradation of MITF. 胡椒碱通过ERK激活和蛋白酶体降解MITF调节黑色素生成
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.4062/biomolther.2024.065
Jun Hyeong Lee, Jieun Lee, Sukanya Dej-Adisai, Jae Sung Hwang
{"title":"Piperine Regulates Melanogenesis through ERK Activation and Proteasomal Degradation of MITF.","authors":"Jun Hyeong Lee, Jieun Lee, Sukanya Dej-Adisai, Jae Sung Hwang","doi":"10.4062/biomolther.2024.065","DOIUrl":"10.4062/biomolther.2024.065","url":null,"abstract":"<p><p>Melanin is a bio-pigment molecule synthesized by melanocytes. Its role is to shield the skin from ultraviolet radiation. Nonetheless, aberrant melanin production, whether excessive or deficient, can lead to conditions such as vitiligo, freckles, melanocytic nevi, and even melanoma. The biosynthetic pathway of melanin is known as melanogenesis, which is regulated by various transcription factors and enzymatic processes. Piperine (PPN), an alkaloid compound extracted from Piper retrofractum Vahl., was investigated for its potential anti-fungal and anti-inflammatory effects. Our hypothesis centered on the inhibition of melanin biosynthesis in response to PPN treatment. Subsequently, it was observed that PPN treatment resulted in a dose-dependent reduction in melanin production, accompanied by a decrease in tyrosinase activity. Furthermore, PPN was found to downregulate the protein levels of key melanogenesis-related genes. Additionally, PPN was observed to elevate the phosphorylation levels of ERK. To assess the role of ERK signaling in PPN-induced melanogenesis regulation, PD98059, an ERK inhibitor, was used. When Melan-A cells were treated with PD98059, the reduced expression level of MITF and melanin content induced by piperine were restored. Additionally, phosphorylation of ERK increased the phosphorylation of MITF at Ser73. This phosphorylated MITF leads to ubiquitination, and ultimately, the protein level of MITF decreases through proteasomal degradation. Likewise, when Melan-A cells were treated with MG132, a proteasomal inhibitor, the reduced expression level of MITF and melanin content induced by piperine were restored. Consequently, PPN can be a potential candidate for application as a skin whitening agent or in formulations to mitigate hyperpigmentation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"408-414"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Daurisoline Inhibits Progression of Triple-Negative Breast Cancer by Regulating the γ-Secretase/Notch Axis. Daurisoline通过调节γ-分泌酶/Notch轴抑制三阴性乳腺癌的进展。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.4062/biomolther.2024.131
Xiangyi Zhan, Xiaoyong Chen, Mei Feng, Kuo Yao, Kefan Yang, Hui Jia
{"title":"Daurisoline Inhibits Progression of Triple-Negative Breast Cancer by Regulating the γ-Secretase/Notch Axis.","authors":"Xiangyi Zhan, Xiaoyong Chen, Mei Feng, Kuo Yao, Kefan Yang, Hui Jia","doi":"10.4062/biomolther.2024.131","DOIUrl":"10.4062/biomolther.2024.131","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from <i>Menispermum dauricum</i>, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated <i>in vitro</i>. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through <i>in vivo</i> experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline's anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects. This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"331-343"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum to "Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin" [Biomol Ther 32(2), 249-260 (2024)]. “膳食中三文鱼鼻软骨蛋白多糖对uvb诱导的光老化皮肤的潜在作用”[生物学报]32(2),249-260(2024)。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 DOI: 10.4062/biomolther.2025.001
Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim
{"title":"Erratum to \"Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin\" [Biomol Ther 32(2), 249-260 (2024)].","authors":"Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim","doi":"10.4062/biomolther.2025.001","DOIUrl":"10.4062/biomolther.2025.001","url":null,"abstract":"","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 2","pages":"415"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isorhamnetin Alleviates Inflammation-Induced Crosstalk between Kynurenine Pathway and Gut Microbiota in Depressed Mice. 异鼠李素减轻抑郁症小鼠犬尿氨酸途径与肠道微生物群之间炎症诱导的串扰。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.4062/biomolther.2024.061
Mengjie Xu, Wei He, Ke Yan, Xinru Gao, Jun Li, Dongyue Xu, Jiao Xiao, Tingxu Yan
{"title":"Isorhamnetin Alleviates Inflammation-Induced Crosstalk between Kynurenine Pathway and Gut Microbiota in Depressed Mice.","authors":"Mengjie Xu, Wei He, Ke Yan, Xinru Gao, Jun Li, Dongyue Xu, Jiao Xiao, Tingxu Yan","doi":"10.4062/biomolther.2024.061","DOIUrl":"10.4062/biomolther.2024.061","url":null,"abstract":"<p><p>Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches <i>in vitro</i> and <i>in vivo</i> and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"297-310"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Allergy Inhibition Using Naturally Occurring Compounds Targeting Thymic Stromal Lymphopoietin Pathways: a Comprehensive Review. 针对胸腺基质淋巴生成素途径的天然化合物的过敏抑制:综合综述。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.4062/biomolther.2024.177
Le Ba Vinh, Kyeong Seon Lee, Yoo Kyong Han, Young Jun Kim, Suzy Kim, Abdul Bari Shah, Youngjoo Byun, Ki Yong Lee
{"title":"Allergy Inhibition Using Naturally Occurring Compounds Targeting Thymic Stromal Lymphopoietin Pathways: a Comprehensive Review.","authors":"Le Ba Vinh, Kyeong Seon Lee, Yoo Kyong Han, Young Jun Kim, Suzy Kim, Abdul Bari Shah, Youngjoo Byun, Ki Yong Lee","doi":"10.4062/biomolther.2024.177","DOIUrl":"10.4062/biomolther.2024.177","url":null,"abstract":"<p><p>Naturally occurring compounds have widely been applied to treat diverse pharmacological effects, including asthma, allergic diseases, antioxidants, inflammation, antibiotics, and cancer. Recent research has revealed the essential role of the thymic stromal lymphopoietin (TSLP) in regulating inflammatory responses at mucosal barriers and maintaining immune homeostasis. Asthma, inflammation, and chronic obstructive pulmonary disease are allergic disorders in which TSLP plays a significant role. Although TSLP's role in type 2 immune responses has undergone comprehensive investigation, its involvement in inflammatory diseases and cancer has also been found to be expanding. However, investigating how to block the TSLP pathway using natural products has been limited. This paper summarizes the roles of various medicinal plants and their chemical components that effectively inhibit the TSLP pathway. In addition, we also highlight the contributions of several plant-derived compounds to treat allergic diseases via targeting TSLP. This review intends to offer innovative concepts to scientists investigating the use of naturally produced compounds and extracts for the treatment of allergic illnesses.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"249-267"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis. 槲皮素-3-甲基醚诱导早期凋亡克服HRV1B免疫逃避,抑制病毒复制,减轻炎症发病机制
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-21 DOI: 10.4062/biomolther.2024.204
Jae-Hyoung Song, Seo-Hyeon Mun, Sunil Mishra, Seong-Ryeol Kim, Heejung Yang, Sun Shim Choi, Min-Jung Kim, Dong-Yeop Kim, Sungchan Cho, Youngwook Ham, Hwa-Jung Choi, Won-Jin Baek, Yong Soo Kwon, Jae-Hoon Chang, Hyun-Jeong Ko
{"title":"Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis.","authors":"Jae-Hyoung Song, Seo-Hyeon Mun, Sunil Mishra, Seong-Ryeol Kim, Heejung Yang, Sun Shim Choi, Min-Jung Kim, Dong-Yeop Kim, Sungchan Cho, Youngwook Ham, Hwa-Jung Choi, Won-Jin Baek, Yong Soo Kwon, Jae-Hoon Chang, Hyun-Jeong Ko","doi":"10.4062/biomolther.2024.204","DOIUrl":"10.4062/biomolther.2024.204","url":null,"abstract":"<p><p>Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from <i>Serratula coronata</i>, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. <i>In vivo</i> administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"388-398"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure-Activity Relationship of NMDA Receptor Ligands and Their Activities on the ERK Activation through Metabotropic Signaling Pathway. NMDA受体配体的构效关系及其对代谢信号通路中ERK激活的影响。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.4062/biomolther.2024.216
Dooti Kundu, Mengling Wang, Suresh Paudel, Shujie Wang, Choon-Gon Jang, Kyeong-Man Kim
{"title":"Structure-Activity Relationship of NMDA Receptor Ligands and Their Activities on the ERK Activation through Metabotropic Signaling Pathway.","authors":"Dooti Kundu, Mengling Wang, Suresh Paudel, Shujie Wang, Choon-Gon Jang, Kyeong-Man Kim","doi":"10.4062/biomolther.2024.216","DOIUrl":"10.4062/biomolther.2024.216","url":null,"abstract":"<p><p>The N-methyl-D-aspartate receptor (NMDA-R) subunit GluN2B is abundantly expressed in brain regions critical for synaptic plasticity and cognitive processes. This study investigated the structure-activity relationships (SAR) of NMDA-R ligands using GluN2B as a molecular target. Thirty potential NMDA-R antagonists were categorized into two structural classes: 1-(1-phenylcyclohexyl) amines (series A) and α-amino-2-phenylcyclohexanone derivatives (series B). In series A compounds, the phenyl ring and R1 substituents were positioned at the carbon center of the cyclohexyl ring, with R2 substituents at the para- or meta-positions of the phenyl ring. SAR analysis revealed optimal binding affinity when R1 was carbonyl (C=O) and R2 was 4-methoxy (4-OMe). Series B compounds featured a cyclohexanone scaffold with NH-R1 at the α-position and a phenyl ring bearing R2 substituents at ortho-, meta-, or para-positions. Maximum binding affinity was achieved with R1 as hydrogen (H) and R2 as hydroxyl (OH). Compounds were assessed for GluN2B-mediated ERK activation to evaluate potential metabotropic signaling properties. Approximately 50% of the compounds demonstrated ERK activation through a non-ionotropic signaling cascade involving Src, phosphatidylinositol 3-kinase, and protein kinase C. This study elucidated key structural determinants for NMDA-R binding and characterized a novel metabotropic signaling pathway. Notably, our findings suggest that compounds acting as antagonists at the ionotropic site may simultaneously function as agonists through non-ionotropic mechanisms.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"278-285"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pro-Oxidative and Inflammatory Actions of Extracellular Hemoglobin and Heme: Molecular Events and Implications for Alzheimer's and Parkinson Disease. 细胞外血红蛋白和血红素的促氧化和炎症作用:阿尔茨海默病和帕金森病的分子事件和意义。
IF 3 3区 医学
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-18 DOI: 10.4062/biomolther.2024.224
Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim
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