Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第3页

Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency. 低纳摩尔效度酮苯并噻唑类肽类TMPRSS13抑制剂的研制。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/14756366.2025.2466841

Alexandre Joushomme, Antoine Désilets, William Champagne, Malihe Hassanzadeh, Gabriel Lemieux, Alice Gravel-Trudeau, Matthieu Lepage, Sabrina Lafrenière, Ulrike Froehlich, Karin List, Pierre-Luc Boudreault, Richard Leduc

{"title":"Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.","authors":"Alexandre Joushomme, Antoine Désilets, William Champagne, Malihe Hassanzadeh, Gabriel Lemieux, Alice Gravel-Trudeau, Matthieu Lepage, Sabrina Lafrenière, Ulrike Froehlich, Karin List, Pierre-Luc Boudreault, Richard Leduc","doi":"10.1080/14756366.2025.2466841","DOIUrl":"10.1080/14756366.2025.2466841","url":null,"abstract":"TMPRSS13, a member of the Type II Transmembrane Serine Proteases (TTSP) family, is involved in cancer progression and in respiratory virus cell entry. To date, no inhibitors have been specifically developed for this protease. In this study, a chemical library of 65 ketobenzothiazole-based peptidomimetic molecules was screened against a proteolytically active form of recombinant TMPRSS13 to identify novel inhibitors. Following an initial round of screening, subsequent synthesis of additional derivatives supported by molecular modelling revealed important molecular determinants involved in TMPRSS13 inhibition. One inhibitor, N-0430, achieved low nanomolar affinity towards TMPRSS13 activity in a cellular context. Using a SARS-CoV-2 pseudovirus cell entry model, we further demonstrated the ability of N-0430 to block TMPRSS13-dependent entry of the pseudovirus. The identified peptidomimetic inhibitors and the molecular insights into their potency gained from this study will aid in the development of specific TMPRSS13 inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2466841"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Promoting collagen synthesis: a viable strategy to combat skin ageing. 促进胶原蛋白合成：对抗皮肤老化的可行策略。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-11 DOI: 10.1080/14756366.2025.2488821

Shan Wang, Feifan Li, Xilong Feng, Meiling Feng, Xiaotian Niu, Xiaoying Jiang, Wenchao Chen, Renren Bai

{"title":"Promoting collagen synthesis: a viable strategy to combat skin ageing.","authors":"Shan Wang, Feifan Li, Xilong Feng, Meiling Feng, Xiaotian Niu, Xiaoying Jiang, Wenchao Chen, Renren Bai","doi":"10.1080/14756366.2025.2488821","DOIUrl":"https://doi.org/10.1080/14756366.2025.2488821","url":null,"abstract":"Skin ageing is a complex physiological process primarily characterised by the deepening of wrinkles and the sagging of the skin. Collagen is essential for maintaining skin elasticity and firmness. As skin ages, it experiences structural and functional changes in collagen, including a decrease in collagen synthesis and an increase in collagen hydrolysis. Thus, promoting collagen synthesis represents a practical strategy for mitigating skin ageing. This review systematically described the functions, classifications and biosynthesis process of collagen, as well as its role in skin ageing. Additionally, the major signalling pathways and targets associated with collagen synthesis were also discussed. More importantly, the review provided a detailed summary of natural products with collagen synthesis-promoting effects and highlighted small molecule compounds with potential anti-ageing activity, especially PPARδ agonists. The relevant content offers potential targets and lead compounds for the development of anti-skin ageing therapies.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2488821"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Design, synthesis and biological evaluation of novel urolithin derivatives targeting liver cancer cells. 针对肝癌细胞的新型尿素衍生物的设计、合成及生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-15 DOI: 10.1080/14756366.2025.2490707

Mi Tian, Lirong Zhao, Yu Lan, Chen Li, Yipeng Ling, Benhong Zhou

{"title":"Design, synthesis and biological evaluation of novel urolithin derivatives targeting liver cancer cells.","authors":"Mi Tian, Lirong Zhao, Yu Lan, Chen Li, Yipeng Ling, Benhong Zhou","doi":"10.1080/14756366.2025.2490707","DOIUrl":"10.1080/14756366.2025.2490707","url":null,"abstract":"We designed and synthesised 22 new urolithin derivatives (UDs) based on methyl-urolithin A (mUA) to identify anti-cancer drugs with high efficacy and low toxicity and evaluated their anti-cancer activities in vitro. Cytotoxicity tests were performed on three cell lines (DU145, T24, and HepG2) and a human normal cell line (HK-2). The half-inhibitory concentration (IC50) of derivative UD-4c to hepatoma HepG2 cells (IC50 = 4.66 ± 0.12 μM) was significantly lower than that of sorafenib (IC50 =7.76 ± 0.12 μM), and exhibited less toxicity to HK-2 cells. Preliminary studies on the mechanism revealed that the derivative UD-4c could significantly inhibit the HepG2 cell growth and colony formation, block the HepG2 cell cycle in the G2/M phase, and induce apoptosis of HepG2 cells dose-dependently. The derivative UD-4c can be used as a potential lead compound to further develop new drugs for hepatocellular carcinoma treatment based on the evaluation of anti-cancer activity.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2490707"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Advances in ERK1/2 inhibition: a medicinal chemistry perspective on structure and regulation. ERK1/2抑制的研究进展：从结构和调控的药物化学角度看。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1080/14756366.2025.2555510

Vimlendu Kumar Sah, Ankit Kumar Singh, Adarsh Kumar, Vineet Prajapati, Amandeep Singh Kalsi, Habibullah Khalilullah, Mariusz Jaremko, Abdul-Hamid Emwas, Amita Verma, Pradeep Kumar

{"title":"Advances in ERK1/2 inhibition: a medicinal chemistry perspective on structure and regulation.","authors":"Vimlendu Kumar Sah, Ankit Kumar Singh, Adarsh Kumar, Vineet Prajapati, Amandeep Singh Kalsi, Habibullah Khalilullah, Mariusz Jaremko, Abdul-Hamid Emwas, Amita Verma, Pradeep Kumar","doi":"10.1080/14756366.2025.2555510","DOIUrl":"10.1080/14756366.2025.2555510","url":null,"abstract":"The mitogen-activated protein kinase (MAPK) pathway-also known as the RAS/RAF/MEK/ERK pathway-is a critical signalling cascade involved in regulating cell growth, proliferation, and survival. First discovered in the early 1980s, the pathway's extracellular signal-regulated kinase (ERK) subfamily was identified in the 1990s. The ERK family includes several isoforms-ERK1, ERK2, ERK3, ERK5, and ERK6-with ERK1 (MAPK3) and ERK2 (MAPK1) being the most well-characterised and playing central roles in MAPK signalling. Deregulation of ERK signalling (commonly referred to as the ERK pathway or ERKp) has been implicated in approximately 40% of human cancers. This review focuses on the structural insights of ERK1/2 and their critical role in the MAPK signalling cascade. Despite their clinical significance, no ERK inhibitors have yet been approved by the FDA. Several molecules-such as SCH772984, SCH900353, ulixertinib (BVD-523), CC-9003, KO-947, AZD0364, norathyriol, and FR180204-are currently in preclinical or clinical trial stages. This review also highlights recent advances in the design and synthesis of ERK inhibitors, emphasising their structural uniqueness and potential to inhibit mutant forms of ERK1/2. Finally, we discuss future directions for the development of ERK1/2 inhibitors as FDA-approved cancer therapeutics.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2555510"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification of a novel pyrrolo[2,3-b]pyridine compound as a potent glycogen synthase kinase 3β inhibitor for treating Alzheimer's disease. 一种新型吡咯[2,3-b]吡啶化合物作为治疗阿尔茨海默病的糖原合成酶激酶3β抑制剂的鉴定。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/14756366.2025.2466846

Qing-Qing Xun, Jing Zhang, Lei Feng, Yu-Ying Ma, Ying Li, Xiao-Long Shi

{"title":"Identification of a novel pyrrolo[2,3-b]pyridine compound as a potent glycogen synthase kinase 3β inhibitor for treating Alzheimer's disease.","authors":"Qing-Qing Xun, Jing Zhang, Lei Feng, Yu-Ying Ma, Ying Li, Xiao-Long Shi","doi":"10.1080/14756366.2025.2466846","DOIUrl":"10.1080/14756366.2025.2466846","url":null,"abstract":"Herein, a novel pyrrolo[2,3-b]pyridine-based glycogen synthase kinase 3β (GSK-3β) inhibitor, S01, was rationally designed and synthesised to target Alzheimer's disease (AD). S01 inhibited GSK-3β, with an IC50 of 0.35 ± 0.06 nM, and had an acceptable kinase selectivity for 24 structurally similar kinases. Western blotting assays indicated that S01 efficiently increased the expression of p-GSK-3β-Ser9 and decreased p-tau-Ser396 levels in a dose-dependent manner. In vitro cell experiments, S01 showed low cytotoxicity to SH-SY5Y cells, significantly upregulated the expression of β-catenin and neurogenesis-related biomarkers, and effectively promoted the outgrowth of differentiated neuronal neurites. Moreover, S01 substantially ameliorated dyskinesia in AlCl3-induced zebrafish AD models at a concentration of 0.12 μM, which was more potent than Donepezil (8 μM) under identical conditions. Acute toxicity experiments further confirmed the safety of S01 in vivo. Our findings suggested that S01 is a prospective GSK-3β inhibitor and can be tested as a candidate for treating AD.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2466846"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Chemical composition, antioxidant activities, and enzyme inhibitory effects of Lespedeza bicolour Turcz. essential oil. 胡枝子的化学成分、抗氧化活性及酶抑制作用。精油。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/14756366.2025.2460053

Jiadong Zhu, Ziyue Xu, Xu Liu

{"title":"Chemical composition, antioxidant activities, and enzyme inhibitory effects of Lespedeza bicolour Turcz. essential oil.","authors":"Jiadong Zhu, Ziyue Xu, Xu Liu","doi":"10.1080/14756366.2025.2460053","DOIUrl":"10.1080/14756366.2025.2460053","url":null,"abstract":"Lespedeza bicolour Turcz. is a traditional medicinal plant with a wide range of ethnomedicinal values. The main components of L. bicolour essential oil (EO) were β-pinene (15.41%), β-phellandrene (12.43%), and caryophyllene (7.79%). The EO of L. bicolour showed antioxidant activity against ABTS radical and DPPH radical with an IC50 value of 0.69 ± 0.03 mg/mL and 10.44 ± 2.09 mg/mL, respectively. The FRAP antioxidant value was 81.96 ± 6.17 μmol/g. The EO had activities against acetylcholinesterase, α-glucosidase, and β-lactamase with IC50 values of 309.30 ± 11.16 μg/mL, 360.47 ± 35.67 μg/mL, and 27.54 ± 1.21 μg/mL, respectively. Molecular docking showed methyl dehydroabietate docked well with all tested enzymes. Sclareol and (+)-borneol acetate showed the strongest binding affinity to α-glucosidase and β-lactamase, respectively. The present study provides a direction for searching enzyme inhibitors for three tested enzymes and shows L. bicolour EO possesses the potential to treat a series of diseases.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2460053"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Discovery of novel dual-targeting inhibitors against PLK1-PBD and PLK4-PB3: structure-guided pharmacophore modelling, virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation. 新型PLK1-PBD和PLK4-PB3双靶向抑制剂的发现：结构引导药效团建模、虚拟筛选、分子对接、分子动力学模拟和生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-15 DOI: 10.1080/14756366.2025.2522810

Changhao Zhao, Hanying Wu, Huajing Liu, Hui Dong, Miao-Miao Niu, Kun Shi, Fengzhen Wang

{"title":"Discovery of novel dual-targeting inhibitors against PLK1-PBD and PLK4-PB3: structure-guided pharmacophore modelling, virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation.","authors":"Changhao Zhao, Hanying Wu, Huajing Liu, Hui Dong, Miao-Miao Niu, Kun Shi, Fengzhen Wang","doi":"10.1080/14756366.2025.2522810","DOIUrl":"10.1080/14756366.2025.2522810","url":null,"abstract":"Aberrant expression of PLK1 and PLK4 is closely associated with tumourigenesis, and their simultaneous inhibition can effectively suppress tumour proliferation. In this study, we successfully identified peptide inhibitors (Peptides 1-5) capable of simultaneously targeting PLK1-PBD and PLK4-PB3 via pharmacophore-based virtual screening. Binding affinity analyses demonstrated that all candidate peptides exhibited nanomolar binding affinity for both targets. In vitro cancer cell growth inhibition assays revealed that these peptides could suppress the growth of cervical cancer cells. Among them, Peptide-2 showed the optimal binding affinity and anticancer cell proliferative activity (PLK1-PBD: Kd = 8.02 ± 0.16 nM; PLK4-PB3: Kd = 11.32 ± 0.19 nM; IC50 = 0.44 ± 0.03). Molecular dynamics (MD) simulations further predicted that Peptide-2 could stably bind to the binding sites of both PLK1-PBD and PLK4-PB3. This study reported a novel peptide inhibitor Peptide-2 with potent dual-target inhibitory activity against PLK1-PBD/PLK4-PB3, providing a novel strategy for cancer therapy.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2522810"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Discovery of lignans as the effective inhibitors of CES1A alleviate lipid droplets formation. 木脂素作为CES1A有效抑制剂的发现减轻了脂滴的形成。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-10 DOI: 10.1080/14756366.2025.2472817

Jie Mu, Si-Si Chen, Shi-Qing Li, Qiang Jin, Jin Geng, Li-Wei Zou

{"title":"Discovery of lignans as the effective inhibitors of CES1A alleviate lipid droplets formation.","authors":"Jie Mu, Si-Si Chen, Shi-Qing Li, Qiang Jin, Jin Geng, Li-Wei Zou","doi":"10.1080/14756366.2025.2472817","DOIUrl":"https://doi.org/10.1080/14756366.2025.2472817","url":null,"abstract":"ER carboxylesterase 1A (CES1A) is an important metabolic enzyme involved in lipid metabolism. Targeting the CES1A is a promising approach for diseases associated with disorders of lipid metabolism therapy. In this study, screening of 26 natural lignans, three of them were found displaying potent inhibition on CES1A and high specificity over other serine hydrolases. Inhibition kinetic analyses demonstrated that Schisandrin C and Anwuligan were mixed-type inhibitors, while Magnolol acts as a competitive inhibitor. Further investigation showed that they were cell permeable and exhibited minimal cytotoxicity and mitochondrial toxicity, as well as capable of inhibiting intracellular CES1A in living cells. Further investigation found that three Schisandras decreased the number of lipid droplets (LDs) in free fatty acid (FFA)-treated HepG2 cells. Collectively, our findings suggest that Schisandrin C is a potent and highly selective inhibitor of CES1A, which can be served as a promising lead compound.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2472817"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Discovery of new aurone derivatives as submicromolar CK2 inhibitors. 发现新的aurone衍生物作为亚微摩尔CK2抑制剂。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1080/14756366.2025.2566780

Mykhailo V Mahdysiuk, Galyna P Volynets, Volodymyr G Bdzhola, Oleksandr A Bieda, Sergiy S Lukashov, Vladislav M Sapelkin, Leonid L Karbovskyi, Sergiy M Yarmoluk

引用次数: 0

Indirubin-3'-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase. 靛玉红-3′-肟作为双作用剂：缓解黑颊果蝇热致雄性不育和抑制可溶性环氧化物水解酶。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-01-22 DOI: 10.1080/14756366.2024.2447719

Nguyen Viet Phong, Hyo-Sung Kim, Yan Zhao, Eunbyul Yeom, Seo Young Yang

{"title":"Indirubin-3'-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase.","authors":"Nguyen Viet Phong, Hyo-Sung Kim, Yan Zhao, Eunbyul Yeom, Seo Young Yang","doi":"10.1080/14756366.2024.2447719","DOIUrl":"10.1080/14756366.2024.2447719","url":null,"abstract":"This study investigated the potential of the indirubin-3'-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restore fertility under heat stress. Additionally, I3O was found to inhibit soluble epoxide hydrolase (sEH), an enzyme involved in the metabolism of epoxyeicosatrienoic acids, which are vital for reproductive health. I3O exhibited sEH inhibitions with an IC50 value of 59.74 ± 0.41 µM. Enzyme kinetics revealed that I3O acts as a non-competitive inhibitor of sEH with a Ki value of 78.88 µM. Molecular docking showed strong interactions between I3O and key residues in the allosteric regions within the sEH enzyme, with a binding affinity of -9.2 kcal/mol. These interactions were supported by 100 ns molecular dynamics simulations, which confirmed the stability of the sEH-I3O complex.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2447719"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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