Drug discoveries & therapeutics最新文献

Telisotuzumab vedotin: The first-in-class c-Met-targeted antibody-drug conjugate granted FDA accelerated approval for treatment of non-squamous non-small cell lung cancer (NSCLC). Telisotuzumab vedotin：首个c- met靶向抗体药物偶联物获得FDA加速批准用于治疗非鳞状非小细胞肺癌（NSCLC）。

Drug discoveries & therapeutics Pub Date : 2025-07-11 DOI: 10.5582/ddt.2025.01058

Chenru Zhao, Daoran Lu, Jianjun Gao

{"title":"Telisotuzumab vedotin: The first-in-class c-Met-targeted antibody-drug conjugate granted FDA accelerated approval for treatment of non-squamous non-small cell lung cancer (NSCLC).","authors":"Chenru Zhao, Daoran Lu, Jianjun Gao","doi":"10.5582/ddt.2025.01058","DOIUrl":"https://doi.org/10.5582/ddt.2025.01058","url":null,"abstract":"Telisotuzumab vedotin represents a clinically important antibody-drug conjugate (ADC) that received accelerated approval from the US Food and Drug Administration in May 2025, establishing it as the first-in-class targeted therapy for adult patients with immunohistochemistry (IHC)-confirmed high-c-Met, EGFR wild-type, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Its mechanism of action relies on precise targeting of the c-Met protein receptor, followed by internalization and release of the potent cytotoxic payload monomethyl auristatin E (MMAE) to eradicate tumor cells. The pivotal phase II LUMINOSITY trial demonstrated that the high c-Met overexpressing group had an overall response rate (ORR) of 34.6%. This therapeutic agent addresses a critical unmet need within a molecularly defined NSCLC subpopulation, marking a substantial advancement in c-Met-targeted oncology. The regulatory authorization and clinical use of telisotuzumab vedotin may significantly advance precision medicine for NSCLC, though an ongoing phase III trial will further confirm its efficacy and safety and determine its eligibility for full regulatory approval in the future.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trpa1 knockout favors colon tumorigenesis in dextran sulfate sodium (DSS)-induced colitis mice. Trpa1基因敲除有利于葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠结肠肿瘤的发生。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-20 DOI: 10.5582/ddt.2025.01022

Fangzhou Dou, Shasha Hu, Daoran Lu, Jianjun Gao

{"title":"Trpa1 knockout favors colon tumorigenesis in dextran sulfate sodium (DSS)-induced colitis mice.","authors":"Fangzhou Dou, Shasha Hu, Daoran Lu, Jianjun Gao","doi":"10.5582/ddt.2025.01022","DOIUrl":"10.5582/ddt.2025.01022","url":null,"abstract":"Chronic inflammation in the colon has been recognized as a key pathogenic mechanism driving colorectal cancer development. TRPA1 (transient receptor potential ankyrin 1), a key member of the TRP cation channel superfamily, is closely implicated in inflammatory processes and has emerged as a promising therapeutic target for anti-inflammatory drug development. However, the precise role of TRPA1 in colorectal carcinogenesis and its potential as a therapeutic target for colorectal cancer (CRC) remain incompletely understood. In this study, we demonstrate that Trpa1 knockout significantly exacerbates DSS-induced colitis-associated tumorigenesis in murine models, a phenomenon mechanistically linked to Trpa1 deficiency-mediated aggravation of inflammatory bowel pathology. RNAseq and gene knockout effect analysis revealed a consistently low expression pattern of TRPA1 across colorectal cancer cell lines (n = 58, median log2(TPM+1) = 0.025), with limited impact on cell viability upon TRPA1 knockout. Notably, analysis of human clinical specimens revealed substantial downregulation of TRPA1 expression in CRC compared to adjacent normal tissues. Kaplan-Meier survival analysis further indicated that patients with TRPA1-low tumors exhibited significantly poorer overall survival outcomes. These collective data suggest a tumor-suppressive role for TRPA1 in colorectal carcinogenesis, potentially through its immunomodulatory functions within the colitis-cancer transformation axis.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"200-207"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quercetin as a multifaceted therapeutic agent in recurrent pregnancy loss: Mechanisms and clinical perspectives. 槲皮素作为复发性妊娠丢失的多层面治疗药物：机制和临床观点。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-29 DOI: 10.5582/ddt.2025.01059

Qing Qi, Jing Zhou, Jing Wang, Yiyuan Zhou, Hongmei Sun, Ling Wang

{"title":"Quercetin as a multifaceted therapeutic agent in recurrent pregnancy loss: Mechanisms and clinical perspectives.","authors":"Qing Qi, Jing Zhou, Jing Wang, Yiyuan Zhou, Hongmei Sun, Ling Wang","doi":"10.5582/ddt.2025.01059","DOIUrl":"10.5582/ddt.2025.01059","url":null,"abstract":"In recent years, there has been an escalating incidence of recurrent pregnancy loss (RPL), imposing substantial psychosocial and economic burdens on families. Despite extensive investigations, approximately 50% of cases remain idiopathic, underscoring the intricate nature of potential pathogenic mechanisms. Quercetin (QUE), a prevalent flavonoid compound, exhibits potential in the therapeutic modulation of RPL by influencing endocrine, coagulation, oxidative stress, inflammation, and immune responses. This review aims to elucidate the potential role of QUE in RPL, explore its molecular mechanisms, and delineate its therapeutic significance. Herein, we synthesize existing evidence on the impact of QUE in RPL, particularly in traditional Chinese medicine, accentuating areas necessitating further exploration. QUE demonstrates regulatory prowess over RPL by modulating endocrine functions, encompassing thyroid functionality, diabetes, polycystic ovary syndrome, and luteal phase defects. It exhibits anti-inflammatory and antioxidant properties, influences coagulation functions, and affects immune cells such as T cells, T helper cells, macrophages, and natural killer cells. QUE also interacts with maternal-fetal interface cells, including myeloid-derived suppressor cells, stromal cells, and extravillous trophoblast cells, highlighting its multifaceted role in the modulation of RPL. Despite promising preclinical data, clinical trials directly targeting RPL remain limited. We emphasize the need for rigorous human studies to validate QUE's efficacy and safety in pregnancy. By elucidating the mechanistic underpinnings of QUE in treating RPL, this research may contribute to developing targeted interventions for RPL and other adverse pregnancy conditions, ultimately ameliorating reproductive health and well-being for affected individuals and families.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"148-159"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Primary cutaneous lymphoma is a microsatellite stable tumor: An analysis of microsatellite instability. 原发性皮肤淋巴瘤是一种微卫星稳定性肿瘤：微卫星不稳定性分析。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-25 DOI: 10.5582/ddt.2025.01042

Saki Maeda-Otsuka, Myangat Tselmeg Mijiddorj, Ikko Kajihara, Soichiro Sawamura, Katsunari Makino, Shinichi Masuguchi, Satoshi Fukushima

引用次数: 0

Abortion adverse events associated with adalimumab, etanercept, ustekinumab, and dupilumab during pregnancy: A pharmacovigilance study based on FDA adverse event reporting system. 妊娠期间与阿达木单抗、依那西普、乌斯特金单抗和杜匹单抗相关的流产不良事件：基于FDA不良事件报告系统的药物警戒研究

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-29 DOI: 10.5582/ddt.2025.01043

Qian Liu, Yang Wang, Panwei Hu, Peizhi He

{"title":"Abortion adverse events associated with adalimumab, etanercept, ustekinumab, and dupilumab during pregnancy: A pharmacovigilance study based on FDA adverse event reporting system.","authors":"Qian Liu, Yang Wang, Panwei Hu, Peizhi He","doi":"10.5582/ddt.2025.01043","DOIUrl":"10.5582/ddt.2025.01043","url":null,"abstract":"Biologics are essential for managing immune-related inflammatory diseases during pregnancy to prevent disease progression and adverse pregnancy outcomes. However, data on the safety of biologics in a broader population are limited. This study aims to evaluate abortion-related adverse events (AEs) associated with adalimumab, etanercept, ustekinumab, and dupilumab, using data from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) to identify signals of abortion-related AEs. The time-to-onset profiles were assessed by analyzing the description and Weibull shape parameters (WSPs) for these events. Sensitivity analyses were also conducted, including drug-drug interaction studies, logistic regression, and a similar retrospective analysis using data from the Japanese Adverse Drug Event Report (JADER) database. Disproportionality analysis revealed specific signals for abortion-related AEs associated with adalimumab, etanercept, and ustekinumab. The drug-drug interaction analysis indicated that these biologics, particularly without methotrexate or prednisolone, increase the risk of abortion-related AEs. Logistic regression identified several factors influencing outcomes. The time-to-onset analysis revealed that dupilumab had an earlier onset of 62.5 days, while etanercept had a later onset at 184 days. WSPs analysis revealed that signals for adalimumab, ustekinumab, and dupilumab exhibited early failure-type features, indicating a decreasing risk of abortion-related AEs over time. In conclusion, adalimumab, etanercept, and ustekinumab are associated with an increased risk of abortion-related adverse pregnancy outcomes, though the signals remain relatively weak. Further large-scale studies are needed to provide more definitive evidence.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"160-173"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acoltremon: The first TRPM8 agonist approved for the treatment of dry eye disease. acoltreon：首个被批准用于治疗干眼症的TRPM8激动剂。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-27 DOI: 10.5582/ddt.2025.01048

Yang Zhou, Wenzhu Zhang, Fusheng Sun

引用次数: 0

Immune modulation and improved systemic performance of phosphate-functionalized nanogels for antifungal therapy. 磷酸盐功能化纳米凝胶抗真菌治疗的免疫调节和改善系统性能。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-27 DOI: 10.5582/ddt.2025.01041

Theresa Vogel, Yidong Yu, Thorsten Keller, Atsushi Miyashita, Lisa Munakata, Ryo Suzuki, Andreas Beilhack, Jürgen Groll, Kazuhisa Sekimizu, Krystyna Albrecht

{"title":"Immune modulation and improved systemic performance of phosphate-functionalized nanogels for antifungal therapy.","authors":"Theresa Vogel, Yidong Yu, Thorsten Keller, Atsushi Miyashita, Lisa Munakata, Ryo Suzuki, Andreas Beilhack, Jürgen Groll, Kazuhisa Sekimizu, Krystyna Albrecht","doi":"10.5582/ddt.2025.01041","DOIUrl":"10.5582/ddt.2025.01041","url":null,"abstract":"Phosphate functionalization of nanogels (NGs), originally designed to enhance interactions with fungal pathogens, also significantly influences their immune interactions and systemic behaviour. In this study, we investigated how phosphate-modified NGs perform as antifungal carriers in vivo using the silkworm model. We found that phosphate functionalization promotes faster internalization by granulocytes-immune cells functionally similar to mammalian neutrophils-highlighting a trade-off between antifungal activity and immune uptake. In parallel, phosphate-functionalized NGs exhibited prolonged circulation, more consistent biodistribution patterns, and reduced batch variability compared to unmodified NGs. These features contributed to superior and more reproducible in vivo antifungal efficacy when delivering itraconazole. Importantly, the biodistribution profiles observed in silkworms aligned well with previous mammalian data, further validating silkworms as an efficient, cost-effective model for early-stage evaluation of nanocarrier systems. Our findings underscore the importance of tuning surface functionalization to balance immune interaction and therapeutic performance, providing valuable insights for optimizing systemic antifungal nanotherapies.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"174-183"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kampo medicine in the management of menopausal symptoms: A narrative review of therapeutic potential. 汉布医学在更年期症状的管理：治疗潜力的叙述回顾。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-25 DOI: 10.5582/ddt.2025.01039

Yuanzheng Liu, Susumu Kobayashi, Ling Wang, Yanming Ren, Peipei Song

{"title":"Kampo medicine in the management of menopausal symptoms: A narrative review of therapeutic potential.","authors":"Yuanzheng Liu, Susumu Kobayashi, Ling Wang, Yanming Ren, Peipei Song","doi":"10.5582/ddt.2025.01039","DOIUrl":"10.5582/ddt.2025.01039","url":null,"abstract":"Menopausal symptoms primarily result from ovarian dysfunction and declining estrogen levels, leading to multisystem disorders. Although hormone therapy remains the most effective treatment, its long-term use is associated with significant risks, prompting interest in alternative options. Kampo medicine, a traditional Japanese system derived from Chinese herbal medicine, has gained renewed attention as a complementary and personalized therapeutic approach to menopausal health. This review aims to systematically summarize the current application and clinical evidence of Kampo medicine in the management of menopausal symptoms across multiple domains, including vasomotor, neuropsychiatric, musculoskeletal, skeletal, and genitourinary systems. Furthermore, the review seeks to further validate its efficacy through the mechanistic actions of its key ingredients. While the therapeutic effects of Kampo medicine on hot flashes have been inconsistent, it has demonstrated significant efficacy in improving emotional disturbances, sleep disorders, and somatic symptoms, particularly among individuals whose conditions are not driven solely by hormonal imbalances. In the management of osteoporosis, the integration of Kampo medicine with conventional Western treatments not only enhances overall therapeutic outcomes but also contributes to the reduction of adverse effects. One limitation of current research is the lack of randomized controlled trials (RCTs) evaluating the efficacy of Kampo medicine in managing Genitourinary Syndrome of Menopause (GSM), highlighting the need for further investigation in this area. The integration of Kampo medicine into menopausal symptom management may contribute to a more holistic, patient-centered approach that offers both traditional and Western medical options. This integrative model has the potential to support shared decision-making and improve personalized care for menopausal women.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"136-147"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The pTau217/Aβ_1-42 plasma ratio: The first FDA-cleared blood biomarker test for diagnosis of Alzheimer's disease. pTau217/ a - β1-42血浆比值：fda批准的首个用于阿尔茨海默病诊断的血液生物标志物测试

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-28 DOI: 10.5582/ddt.2025.01055

Shasha Hu, Haizhou Yu, Jianjun Gao

{"title":"The pTau217/Aβ1-42 plasma ratio: The first FDA-cleared blood biomarker test for diagnosis of Alzheimer's disease.","authors":"Shasha Hu, Haizhou Yu, Jianjun Gao","doi":"10.5582/ddt.2025.01055","DOIUrl":"10.5582/ddt.2025.01055","url":null,"abstract":"As the most prevalent form of dementia, Alzheimer's disease (AD) represents a major public health challenge. Early diagnosis is crucial to delaying disease progression, and yet the gold standard for detection of biomarkers - cerebral positron emission tomography (PET) imaging and cerebrospinal fluid biomarker analysis - is constrained by invasiveness, high costs, and limited accessibility. On May 16, 2025, the FDA granted its first clearance to the Lumipulse G blood test, which utilizes the plasma pTau217/Aβ1-42 ratio, for the diagnosis of amyloid plaques in symptomatic patients age 55 or older. In clinical validation, concordance rates with amyloid PET brain scans/the results of cerebrospinal fluid biomarker detection were 91.7% (positive) and 97.3% (negative). Similar blood-based assays have previously been approved in Japan (HISCL™ Aβ42/40), the United Kingdom (PrecivityAD2™), and China. While concerns regarding false-positive/false-negative rates necessitate continued attention and their role as adjunctive diagnostic tools requires integration with comprehensive clinical assessment and other tests, the rapid development and regulatory clearance of these blood-based biomarker assays undeniably offer promising prospects for transforming the diagnostic and therapeutic paradigm for AD.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"208-209"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opsin 3-mediated regulation of blue light-induced β-hexosaminidase release from mast cells. 视蛋白3介导的蓝光诱导肥大细胞释放β-己糖氨酸酶的调控。

Drug discoveries & therapeutics Pub Date : 2025-07-04 Epub Date: 2025-06-25 DOI: 10.5582/ddt.2025.01035

Hiroyuki Yamamoto, Miki Kiryu, Yoshikazu Sawaguchi, Toshiyuki Yamada

{"title":"Opsin 3-mediated regulation of blue light-induced β-hexosaminidase release from mast cells.","authors":"Hiroyuki Yamamoto, Miki Kiryu, Yoshikazu Sawaguchi, Toshiyuki Yamada","doi":"10.5582/ddt.2025.01035","DOIUrl":"10.5582/ddt.2025.01035","url":null,"abstract":"The human body is constantly exposed to light from the environment, and intense light is a source of skin inflammation. Although cellular responses to high-energy ultraviolet light have long been reported, the photoresponsive mechanism occurring after skin exposure to visible light remains unclear. This study focused on mast cells involved in inflammation and examined the expression of photoreceptors and their effects on degranulation in mast cells. Photoreceptors expressed in two mast cell cultures (P-815 and RBL-2H3) were examined by RT-PCR and western blotting to demonstrate that OPN3 was expressed in RBL-2H3 cells. Next, the effect of visible light exposure on degranulation was evaluated by measuring β-hexosaminidase activity in the culture medium. The results show that β-hexosaminidase release was most strongly induced at wavelengths of ~460 nm, which corresponds to the absorption peak of OPN3. In addition, suppression of OPN3 expression by siRNA reduced β-hexosaminidase release at 460 nm. These results suggest that OPN3 expressed in mast cells mediates degranulation in skin inflammation that occurs upon exposure to intense light.","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"184-188"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0