Biologics : Targets & Therapy最新文献

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Teclistamab for Relapsed or Refractory Multiple Myeloma: A Review of Efficacy, Safety, Resistance Mechanisms and Future Directions. 替司他抗治疗复发或难治性多发性骨髓瘤:疗效、安全性、耐药机制和未来发展方向综述
IF 3.4
Biologics : Targets & Therapy Pub Date : 2026-01-13 eCollection Date: 2026-01-01 DOI: 10.2147/BTT.S539066
Bénédicte Piron, Philippe Moreau, Cyrille Touzeau
{"title":"Teclistamab for Relapsed or Refractory Multiple Myeloma: A Review of Efficacy, Safety, Resistance Mechanisms and Future Directions.","authors":"Bénédicte Piron, Philippe Moreau, Cyrille Touzeau","doi":"10.2147/BTT.S539066","DOIUrl":"10.2147/BTT.S539066","url":null,"abstract":"<p><p>Teclistamab is the first bispecific antibody targeting B-cell maturation antigen (BCMA) approved for the treatment of relapsed or refractory multiple myeloma. Its significant efficacy as monotherapy, particularly in the Phase 1/2 MajesTEC-1 trial, has been also confirmed in the context of combination therapies. Early safety events are dominated by grade 1 or 2 cytokine release syndrome. Risk of infection is now better characterized and can be managed through systematic prophylaxis. Notably, real-world studies have confirmed its efficacy and safety, notably in patients under-represented or ineligible for clinical trials (elderly, with renal impairment or central nervous system involvement). Mechanisms of resistance to teclistamab including target loss and T-cell environment are increasingly understood. Consequently, several strategies to overcome immune escape or antigen loss are currently being evaluated in clinical trials. The use of teclistamab in earlier lines of treatment and in combination may yield better results and is evaluating but ongoing Phase 3 clinical trials.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"539066"},"PeriodicalIF":3.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research on the Role of Autophagy in Vascular Endothelial Cells in the Healing of Chronic Refractory Wounds. 血管内皮细胞自噬在慢性难治性伤口愈合中的作用研究。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2026-01-13 eCollection Date: 2026-01-01 DOI: 10.2147/BTT.S573844
Lao Riling, Fan Kunyue, Gan Liyan, Wang Yaya, Ni Baoling, Li Jiehui
{"title":"Research on the Role of Autophagy in Vascular Endothelial Cells in the Healing of Chronic Refractory Wounds.","authors":"Lao Riling, Fan Kunyue, Gan Liyan, Wang Yaya, Ni Baoling, Li Jiehui","doi":"10.2147/BTT.S573844","DOIUrl":"https://doi.org/10.2147/BTT.S573844","url":null,"abstract":"<p><p>Chronic refractory wounds exhibit a complex etiology characterized by prolonged healing and pathological chronic inflammation, which pose significant challenges to wound recovery and may increase the risk of cancer over time. In recent years, the autophagy mechanism has emerged as a focal point of research. This process is regulated by nutritional status, growth factors, and cellular stress. Autophagy facilitates the removal of damaged organelles and misfolded proteins, recycles nutrients, contributes to immune defense, and aids in the elimination of pathogens. Endothelial autophagy is particularly crucial in the healing of chronic refractory wounds. It may be activated under conditions of ischemia, hypoxia, inflammation, and infection, thereby inhibiting cell proliferation and tissue repair while assisting cells in maintaining homeostasis and managing various stressors. Consequently, investigating the autophagic mechanisms in vascular endothelial cells during chronic refractory wound healing is essential for the development of novel wound treatment strategies.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"573844"},"PeriodicalIF":3.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal Stem Cell Therapy in Osteoarthritis and Rheumatoid Arthritis: A Systematic Review of Exosomal microRNAs. 骨关节炎和类风湿关节炎的间充质干细胞治疗:外泌体microRNAs的系统综述。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-12-30 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S571417
Seyyed Sina Hejazian, Seyyedeh Mina Hejazian, Seyede Saba Mostafavi Montazeri, Sima Abediazar, Sepideh Zununi Vahed, Abolfazl Barzegari
{"title":"Mesenchymal Stem Cell Therapy in Osteoarthritis and Rheumatoid Arthritis: A Systematic Review of Exosomal microRNAs.","authors":"Seyyed Sina Hejazian, Seyyedeh Mina Hejazian, Seyede Saba Mostafavi Montazeri, Sima Abediazar, Sepideh Zununi Vahed, Abolfazl Barzegari","doi":"10.2147/BTT.S571417","DOIUrl":"10.2147/BTT.S571417","url":null,"abstract":"<p><strong>Summary: </strong>Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic diseases characterized by persistent inflammation and autoimmune responses that affect the joints and other organs. Scientific evidence indicates that the therapeutic effects of mesenchymal stem cells (MSCs) are mediated through the release of soluble factors and extracellular vesicles (EVs), particularly exosomes. The release of microRNAs from MSCs holds substantial potential for cell-free treatment in OA and RA.</p><p><strong>Methods: </strong>A comprehensive search was conducted on Web of Science, PubMed, Scopus, and Google Scholar to identify relevant publications until 24 March 2024. The systematic review aimed at illuminating the current understanding of MSC-derived exosomal microRNAs, the origin of MSCs, potential mechanisms of action, and their therapeutic implications in managing OA and RA.</p><p><strong>Results: </strong>A total of fifty-five articles (OA, n= 41 and RA, n= 14) were deemed eligible for inclusion in this study. Regardless of MSC origin, exosomal miRNAs could induce anti-inflammatory, protective, and chondroregenerative potential in in vitro and in vivo models of OA by targeting different signaling pathways. Fourteen studies have highlighted the role of MSC-derived exosomal miRNAs in modulating immune responses, reducing pro-inflammatory cytokine production, and potentially ameliorating synovial inflammation and joint symptoms associated with RA. To suppress joint inflammation and preserve cartilage, miR-140, miR-92a-3p, and miR-136-5p emerged as leading candidates for OA because they help restore the anabolic/catabolic balance and modulate key signaling pathways. For RA, the most effective candidates were miR-146a, miR-150-5p and miR-205-5p that target innate and adaptive immune signaling and synoviocyte activation, with NF-κB modulators such as miR-361-5p offering overlap across both diseases.</p><p><strong>Conclusion: </strong>The mounting body of preclinical evidence supports that MSC-exosomal-miRNAs present a promising solution for OA and RA as a novel therapeutic strategy. However, human studies and more clinical trials are warranted.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"747-785"},"PeriodicalIF":3.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing [Corrigendum]. 勘误:CRISPR/ cas9介导的基因组编辑的机制和应用[勘误]。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-12-27 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S585961
{"title":"Erratum: Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing [Corrigendum].","authors":"","doi":"10.2147/BTT.S585961","DOIUrl":"https://doi.org/10.2147/BTT.S585961","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/BTT.S326422.].</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"745-746"},"PeriodicalIF":3.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12757175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy, Safety, and Cost-Effectiveness of the Infliximab Biosimilar GP-1111 in Patients with Inflammatory Bowel Disease Who Underwent a Nonmedical Switch: A Prospective Cohort Study. 英夫利昔单抗生物仿制药GP-1111在炎症性肠病患者非药物转换中的疗效、安全性和成本效益:一项前瞻性队列研究
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-12-18 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S559503
Máté Pápista, Tamás Resál, Péter Bacsur, Diána Kata, Bernadett Farkas, Anita Bálint, Anna Fábián, Renáta Bor, Emese Ivány, Zoltán Szepes, Klaudia Farkas, Zoltán Juhász, Norbert Buzás, Tamás Molnár
{"title":"Efficacy, Safety, and Cost-Effectiveness of the Infliximab Biosimilar GP-1111 in Patients with Inflammatory Bowel Disease Who Underwent a Nonmedical Switch: A Prospective Cohort Study.","authors":"Máté Pápista, Tamás Resál, Péter Bacsur, Diána Kata, Bernadett Farkas, Anita Bálint, Anna Fábián, Renáta Bor, Emese Ivány, Zoltán Szepes, Klaudia Farkas, Zoltán Juhász, Norbert Buzás, Tamás Molnár","doi":"10.2147/BTT.S559503","DOIUrl":"10.2147/BTT.S559503","url":null,"abstract":"<p><strong>Purpose: </strong>Data regarding treatment switch from the originator infliximab (IFX) to GP-1111 in inflammatory bowel disease (IBD) are limited. Only a few studies have examined the financial aspects of biosimilar use, none of them regarding GP-1111. The study aimed to evaluate the long-term efficacy and safety of the IFX biosimilar GP-1111 in patients with IBD who underwent a nonmedical switch from the original IFX in real-life settings. Further, it investigated the switch from a health economics perspective.</p><p><strong>Patients and methods: </strong>A prospective cohort study was conducted on patients with IBD who were on maintenance IFX treatment and who switched to the IFX biosimilar GP-1111 due to financial constraints, with a 1-year follow-up period. Clinical and laboratory parameters were measured at baseline and at weeks 8, 16, and 52 and serum IFX levels were measured at baseline and at week 24. Statistical analyses were performed using the paired <i>t</i>-test, Pearson's chi-square test, Kaplan-Meier survival curves, Cox proportional hazard regression models, and univariate linear model.</p><p><strong>Results: </strong>This study included 142 patients (95 with Crohn's disease and 47 with ulcerative colitis). The average serum IFX level remained within the therapeutic range from baseline (3.2 ± 2.3 μg/mL) to week 24 (3.7 ± 2.7 μg/mL, p = 0.106). The corticosteroid-free remission (S-SFR) rates were stable (baseline: 69.7%, follow-up: 72.9%, p = 0.58). The 1-year treatment persistence rate was 83.1%. The adverse events included allergic reactions (IR: 6.3 per 100 patient-years) and paradoxical reactions (IR: 2.4 per 100 patient-years). Based on the estimated cost analysis, biosimilar use could lead to significant savings, with a total of 201.9 million HUF (514,000 €).</p><p><strong>Conclusion: </strong>The IFX biosimilar GP-1111 was safe and effective against IBD in real-world settings. The average serum IFX levels and S-SFR rates remained stable, while no identifiable factors leading to treatment discontinuation were observed. Biosimilar use has a cost advantage with a reassuring safety profile.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"731-743"},"PeriodicalIF":3.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: LncRNA GAS5 Modulates the Progression of Glioma Through Repressing miR-135b-5p and Upregulating APC [Corrigendum]. LncRNA GAS5通过抑制miR-135b-5p和上调APC调节胶质瘤的进展[勘误]。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-12-10 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S586794
{"title":"Erratum: LncRNA GAS5 Modulates the Progression of Glioma Through Repressing miR-135b-5p and Upregulating APC [Corrigendum].","authors":"","doi":"10.2147/BTT.S586794","DOIUrl":"https://doi.org/10.2147/BTT.S586794","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/BTT.S454058.].</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"729-730"},"PeriodicalIF":3.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Switch from Intravenous to Subcutaneous Formulation of Tocilizumab in Rheumatoid Arthritis: Retrospective Cohort Analysis and Systematic Literature Review. 从静脉注射到皮下注射Tocilizumab治疗类风湿关节炎:回顾性队列分析和系统文献综述
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-12-04 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S555169
Giorgio Galoppini, Carlo Garaffoni, Andrea Lotesoriere, Federico Nogarin, Alessandra Bortoluzzi, Marcello Govoni, Ettore Silvagni
{"title":"Switch from Intravenous to Subcutaneous Formulation of Tocilizumab in Rheumatoid Arthritis: Retrospective Cohort Analysis and Systematic Literature Review.","authors":"Giorgio Galoppini, Carlo Garaffoni, Andrea Lotesoriere, Federico Nogarin, Alessandra Bortoluzzi, Marcello Govoni, Ettore Silvagni","doi":"10.2147/BTT.S555169","DOIUrl":"10.2147/BTT.S555169","url":null,"abstract":"<p><strong>Purpose: </strong>Subcutaneous tocilizumab (SC-TCZ) is approved for rheumatoid arthritis (RA) management. During Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) pandemics, experiences of intravenous (IV)-to-SC TCZ switch in RA patients spread. We aimed to determine SC-TCZ maintenance, efficacy and safety in IV-to-SC TCZ switchers, combining a single center, retrospective cohort study and a systematic literature review (SLR).</p><p><strong>Patients and methods: </strong>We included RA patients undergoing IV-to-SC TCZ switch (2015-2024); patients were grouped and evaluated according to maintenance of SC-TCZ (\"Go on SC\" group, GoS) or returning to IV-TCZ within 12 months (T2) (\"Back IV\" group, BI). SC-TCZ maintenance, disease activity, adverse events (AEs) were evaluated; a univariate regression analysis was performed to evaluate factors associated with a successful switch. The SLR was performed in accordance with PRISMA 2.0 guidelines and registered in PRSPERO (ID CRD42024523714), to search for relevant articles regarding maintenance of SC-TCZ after IV-to-SC switch, efficacy (assessed both clinically and with clinimetric tools) and safety of this strategy, as well as predictors of a successful IV-to-SC switch.</p><p><strong>Results: </strong>According to the success of SC-TCZ switch (T2), SC-TCZ maintenance rate was 43.3% (13/30 patients). A switch back to IV-TCZ was more likely if patients had higher baseline GH score (OR 1.05, 95% CI 1.01-1.10), and less likely if the IV-to-SC switch was agreed with treating physician (0.03, 0.00-0.21). At first visit after baseline, the mean DAS28 value diminished in GoS (-0.3) versus BI (+0.5), p < 0.001. No treatment-related serious AEs were reported. The SLR retrieved 12 articles (3626 patients), including 2 open-label randomized controlled trials (RCTs) and 10 observational studies. By the end of follow-up, SC-TCZ maintenance in our cohort was lower than in other experiences (25.9% versus 78.7%), but with a longer follow-up (up to 4.5 years).</p><p><strong>Conclusion: </strong>Intravenous to subcutaneous tocilizumab switch is an effective and safe option in rheumatoid arthritis management, especially in the case of a shared decision.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"713-727"},"PeriodicalIF":3.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12684985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor-to-Tumor Metastasis: Breast Cancer Metastasizing to EGFR Exon 19-Mutated Lung Adenocarcinoma with Long-Term Disease-Free Survival. 肿瘤到肿瘤转移:乳腺癌转移到EGFR外显子19突变的肺腺癌,长期无病生存。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-11-19 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S558828
Yana Zhang, Yang Hao, Han Yang, Xiangli Meng, Shanshan Yang, Jin Wang, Jinling Xie, Ping Lu, Yinghua Ji
{"title":"Tumor-to-Tumor Metastasis: Breast Cancer Metastasizing to EGFR Exon 19-Mutated Lung Adenocarcinoma with Long-Term Disease-Free Survival.","authors":"Yana Zhang, Yang Hao, Han Yang, Xiangli Meng, Shanshan Yang, Jin Wang, Jinling Xie, Ping Lu, Yinghua Ji","doi":"10.2147/BTT.S558828","DOIUrl":"10.2147/BTT.S558828","url":null,"abstract":"<p><p>Tumor-to-tumor metastasis (TTM) is a rare phenomenon characterized by the metastasis of one malignant tumor into another histologically different tumor. While breast and lung cancers are prevalent among women globally, TTM involving breast cancer metastasizing to lung adenocarcinoma is exceptionally uncommon. Herein, we report a rare case of Luminal B breast cancer metastasizing to EGFR exon 19 deletion-mutated lung adenocarcinoma. The patient achieved prolonged disease-free survival following comprehensive treatment, including surgical resection, chemotherapy, EGFR-tyrosine kinase inhibitor (TKI) therapy, and endocrine therapy. This case highlights the importance of molecular profiling in guiding personalized therapeutic strategies for TTM, particularly when actionable mutations are present.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"707-712"},"PeriodicalIF":3.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12640590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Silico Screening of Streptomyces sp. Metabolites Targeting P. falciparum DHODH and DPCK for Antimalarial Discovery. 针对恶性疟原虫DHODH和DPCK的链霉菌代谢物抗疟发现的计算机筛选
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-11-15 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S539147
Syeftyan Muhammad Ali Hamami, Faris Rega Riswana, Loeki Enggar Fitri, Nashi Widodo, Muhammad Nizam Zulfi Zakaria, Ahmad Fariduddin Aththar, Elvina Rashida Khairi, Abdullah Abdullah, Dymas Yoga Prasetya, Michelle Fai
{"title":"In Silico Screening of <i>Streptomyces</i> sp. Metabolites Targeting <i>P. falciparum</i> DHODH and DPCK for Antimalarial Discovery.","authors":"Syeftyan Muhammad Ali Hamami, Faris Rega Riswana, Loeki Enggar Fitri, Nashi Widodo, Muhammad Nizam Zulfi Zakaria, Ahmad Fariduddin Aththar, Elvina Rashida Khairi, Abdullah Abdullah, Dymas Yoga Prasetya, Michelle Fai","doi":"10.2147/BTT.S539147","DOIUrl":"10.2147/BTT.S539147","url":null,"abstract":"<p><strong>Background: </strong>Malaria is a major global health issue, which significantly affects developing countries, including Indonesia. <i>Plasmodium falciparum</i>, the leading cause of malaria mortality, is increasingly resistant to standard treatments. The antimalarial properties of compounds derived from <i>Streptomyces</i> sp. have been demonstrated in several in vivo and in vitro studies, although their exact mechanism of action remains unclear. This study explores <i>Streptomyces</i> sp. metabolites as potential antimalarials targeting <i>Pf</i>DHODH and <i>Pf</i>DPCK, essential enzymes for <i>P. falciparum</i> survival.</p><p><strong>Methods: </strong>A comprehensive in silico screening was employed, including phylogenetic analysis of <i>Pf</i>DHODH and <i>Pf</i>DPCK, network protein analysis, identification and preparation of <i>Streptomyces</i> sp. bioactive compounds, structural preparation of target enzymes, molecular docking and visualization, antimalarial efficacy prediction, assessment of drug-likeness and toxicity, and molecular dynamics simulations.</p><p><strong>Results: </strong>Phylogenetic analysis confirmed that <i>Pf</i>DHODH and <i>Pf</i>DPCK are distinct from human proteins, reducing off-target risks. Network analysis identified nine proteins linked to <i>Pf</i>DHODH and one for <i>Pf</i>DPCK. From 27 <i>Streptomyces</i> sp. bioactive compounds, caboxamycin, bisanhydroaklavinone, napyradiomycin A1, and gardenomycin A showed the strongest binding to target enzymes. These compounds occupied the active sites of <i>Pf</i>DHODH and <i>Pf</i>DPCK, mirroring control ligands (FMN, Opera1). PASS analysis indicated strong antiprotozoal potential for bisanhydroaklavinone and gardenomycin A. Toxicity analysis revealed bisanhydroaklavinone's mutagenicity and carcinogenicity risks, while napyradiomycin A1 showed moderate hepatotoxicity. Nonetheless, molecular dynamics confirmed stable interactions, highlighting their promise as antimalarial candidates. However, their toxicity profiles warrant further investigation to ensure safe therapeutic application.</p><p><strong>Conclusion: </strong><i>Pf</i>DHODH and <i>Pf</i>DPCK were identified as selective targets in <i>P. falciparum</i>. Four <i>Streptomyces</i>-derived compounds showed strong binding, stability, and promising antimalarial potential with acceptable predicted toxicity, warranting further evaluation. However, only caboxamycin and gardenomycin show potential for antimalarial drug development, with acceptable predicted toxicity profiles, making them suitable candidates for in vitro and in vivo testing prior to clinical evaluation.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"681-705"},"PeriodicalIF":3.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12630009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond Monotherapy: Exploring the Efficacy and Safety of Dual Biologic Strategies in Rheumatic Diseases. 超越单药治疗:探索双生物策略在风湿病中的疗效和安全性。
IF 3.4
Biologics : Targets & Therapy Pub Date : 2025-11-08 eCollection Date: 2025-01-01 DOI: 10.2147/BTT.S565137
Fadi Hassan, Helana Jeries, Rula Daood, Mohammad E Naffaa
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