若生智能
Drug Database
FL

fluorouracil (Carac, microsponge)

✓ Approved

Heron Therapeutics, Inc. · TYMS · 小分子

什么是 fluorouracil？

fluorouracil 是一种小分子，由Heron Therapeutics, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Transdermal。

药物档案

商品名Carac, microsponge
公司Heron Therapeutics, Inc.
药物类别小分子
分子靶点TYMS
给药途径Transdermal
状态Approved
来源： ClinicalTrials.gov, Heron Therapeutics, Inc.

作用机制

分子靶点

fluorouracil 作用于 1 个分子靶点：

TYMSthymidylate synthetase (DKCD, TMS)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

fluorouracil 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Skin and subcutaneous tissue disordersActinic keratosis✓ Approved

相关研究文献

PubMedGut microbes2026-06-13

Muribaculum as a microbial contributor of rifaximin-induced mucosal protection during chemotherapy.

Correale Carmen C, Morandi Martina M, Gil-Gomez Antonio A, Silvestri Alessandra A et al.

Chemotherapy-induced intestinal mucositis is a frequent and dose-limiting toxicity that compromises cancer treatment outcomes and lacks effective targeted interventions. Here, we investigate the mechanisms by which the nonabsorbable antibiotic rifaximin mitigates chemotherapy-induced intestinal injury, focusing on microbiota-mediated preservation of epithelial barrier integrity. In a murine model of 5-fluorouracil (5-FU)-induced intestinal injury, rifaximin pretreatment reduced mucosal inflammation and tissue damage, preserved epithelial and mucus barrier integrity, and limited systemic endotoxemia. Importantly, rifaximin did not impair the antitumor efficacy of 5-FU in ApcMin/+C3arKO mice. To assess translational relevance, we employed a human intestinal ex vivo organ culture system (EVOC) and found that rifaximin preserved mucosal architecture, mucus balance, and tight junction integrity following inflammatory challenge. Microbiome profiling revealed that rifaximin reshaped the intestinal microbial community, preventing the depletion of health-associated taxa, including Muribaculum and Parasutterella. Functional experiments demonstrated that Muribaculum intestinale supplementation alone attenuated 5-FU-induced injury, reproducing key protective features of rifaximin treatment. Together, these findings identify Muribaculum as a microbial contributor to rifaximin's protective effects, supporting its potential role as a safe adjunctive strategy to improve gastrointestinal tolerability of cancer treatment.

PMID 42286866
阅读全文 →
PubMedCellular signalling2026-06-13

ARTN drives ABCB1-mediated chemoresistance in gastric cancer cells by promoting ELK4 phosphorylation.

Wang Xiaolong X, Jin Guixiu G, Cheng Zhirong Z, Sang Yongyong Y et al.

Chemoresistance is the primary hindrance to effective gastric cancer (GC) treatment. Artemin (ARTN) exerts oncogenic roles in various malignancies (including GC), yet its involvement in GC chemoresistance remains unelucidated. This work sought to clarify the function of ARTN and the mechanism in GC chemoresistance. ARTN expression was detected via qPCR and western blotting. The functions of ARTN in GC chemoresistance were evaluated in vitro by CCK-8, apoptosis, and colony formation assays, which were also determined in vivo using a xenograft mouse model. Immunohistochemistry was adopted to measure Ki67 (a marker of proliferation) and cleaved caspase 3 (a marker of apoptosis) in tumor tissues. ELK4 phosphorylation was assessed through immunoprecipitation and western blotting. ChIP-qPCR was employed to determine the binding of ELK4 and ABCB1. ARTN was aberrantly upregulated in GC cells, particularly in chemo-resistant GC cells; its knockdown efficaciously sensitized chemo-resistant GC cells to 5-fluorouracil (5-FU), reduced proliferation, and enhanced apoptosis. In vivo, ARTN deficiency restrained tumor growth in chemo-resistant xenograft mice under 5-FU treatment, with downregulated Ki67 and upregulated cleaved caspase 3 in tumor tissues. Molecular mechanism experiments revealed that ARTN facilitated ELK4 phosphorylation and increase ABCB1 expression in GC cells by activating KRAS/ERK signaling. Crucially, ARTN overexpression impaired GC cell sensitivity to 5-FU in vitro, which was abrogated by ELK4 or ABCB1 knockdown. ARTN promotes GC chemoresistance by upregulating ABCB1 expression via modulating ELK4 phosphorylation, offering a likely therapeutic approach to reverse GC chemoresistance.

PMID 42285190
阅读全文 →
PubMedNutrients2026-06-12

Dual-Protein Intervention in CT26 Tumor-Bearing Mice: A Preliminary Evaluation of Its Effects on Anti-Tumor Efficacy of 5-Fluorouracil and Immune Responses.

Feng Duo D, Li Mengjie M, Han Di D, Ma Menghan M et al.

Colorectal cancer is a common malignancy and 5-fluorouracil (FU) remains a mainstay of chemotherapy despite its toxicity. As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention. This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP. The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4+ T and CD8+ T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-γ and decrease IL-6 and TNF-α. In conclusion, a moderate dose (0.67 g/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes.

PMID 42280307
阅读全文 →
PubMedCancer chemotherapy and pharmacology2026-06-12

Model-based meta-analysis of individual patient data for the characterization of intravenous 5-fluorouracil population pharmacokinetics.

Briki Myriam M, Thoueille Paul P, Joerger Markus M, Chatelut Etienne E et al.

The pharmacokinetics (PK) of 5-fluorouracil (5-FU) has been thoroughly studied over the past decades. Using an individual patient data model-based meta-analysis (IPD-MBMA) approach, this study aims to build a generalized model by combining IPD from multiple studies, investigating the role of lean body mass (LBM) in 5-FU PK, and exploring a model informed precision dosing (MIPD)-based approach for refining its therapeutic drug monitoring (TDM). Raw PK data from three 5-FU PK studies (726 patients, 2,332 plasma concentrations) were harmonized and grouped into one homogeneous dataset, preserving traceability to the original data source. An overall population PK (popPK) model for intravenous 5-FU was developed using nonlinear mixed-effects modeling (NONMEM). A two-compartment model with both saturable (Michaelis-Menten elimination; Vmax, Km) and linear elimination (CL) best described 5-FU disposition, with a stratified error model to capture between-study differences. Body-surface area (BSA) significantly impacted CL, and Vmax was 15% lower in women and decreased with age. In a parallel analysis, the sex effect on Vmax was translated into an LBM effect, with metabolic capacity increasing with LBM. Based on a 12-cycle simulation, after 4 cycles of TDM-based dose adjustment, 95% of the patient should be optimally exposed in the context of colorectal cancer (area under the curve, AUC 20-29 mg∙h/L). A virtual MIPD-based approach predicted higher target attainment after one adjustment (70 - 68%) compared to classic TDM predictions (49-59%) in men and women, respectively. Finally, the administration of a bolus before the continuous infusion of 5-FU is not expected to materially affect its subsequent continuous infusion AUC. Aggregating IPD enables building more generalizable popPK models while accommodating study-specific residual variability; broader raw-data sharing would strengthen current evidence and reveal remaining gaps. For 5-FU, BSA dosing leaves substantial interpatient variability, so LBM-based and model-informed strategies, including a priori dosing and MIPD-assisted TDM, warrant prospective evaluation.

PMID 42283826
阅读全文 →
PubMedInternational journal of molecular sciences2026-06-12

ABCG2 Contributes to Multidrug Resistance and Aggressive Phenotypes Associated with ERK Signaling in Gastric Cancer.

Türksoy Terzioğlu Özlem Ö, Terzioğlu Gökhan G

Multidrug resistance remains a major obstacle in gastric cancer therapy and is frequently associated with aggressive phenotypes. Although ABCG2 is a well-known drug efflux transporter, its functional contribution to paclitaxel (PTX) resistance and its relationship with ERK signaling in gastric cancer remain incompletely understood. In this study, PTX-resistant gastric cancer cell models were established through prolonged drug exposure. Resistant cells exhibited cross-resistance to cisplatin and 5-fluorouracil together with enhanced drug efflux activity, invasion capacity, spheroid formation, stemness-associated marker expression, and G0/G1 enrichment. ABCG2 expression was markedly increased in resistant cells. Stable knockdown of ABCG2 restored PTX sensitivity and significantly reduced drug efflux, invasion, spheroid formation, and stemness-associated phenotypes, while increasing apoptosis and altering cell cycle distribution. ABCG2 depletion was associated with reduced ERK phosphorylation and decreased expression of ERK downstream target genes. Pharmacological inhibition of ERK signaling similarly suppressed resistance-associated phenotypes and reduced ABCG2 expression. Whereas reactivation of ERK signaling by constitutively active MEK1 partially rescued the effects of ABCG2 depletion, restoring aggressive and multidrug-resistant phenotypes. Our findings indicate that ERK signaling functionally contributes to ABCG2-associated multidrug resistance and aggressive phenotypes in PTX-resistant gastric cancer cells.

PMID 42278563
阅读全文 →
PubMedCancers2026-06-12

Molecular Characterization of Small Extracellular Vesicles in Pancreatic Cancer Patients Treated with Neoadjuvant Chemotherapy Followed by Stereotactic Body Radiation.

Paluri Ravi Kumar RK, Kumar Ashish A, Su Yixin Y, Singh Sangeeta S et al.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited therapeutic options, a high mortality rate, and poor overall survival, necessitating the development of new therapeutic and diagnostic strategies. This study investigated the potential of plasma-derived small extracellular vesicles (sEVs) as a source of molecular biomarkers associated with the treatment response. Methods: Plasma samples were obtained from patients with locally advanced and borderline resectable PDAC at baseline and following neoadjuvant chemotherapy, either FOLFIRINOX (5-FU [fluorouracil], leucovorin, oxaliplatin, and irinotecan) or GEM-ABRAX ( gemcitabine plus nab-paclitaxel), followed by stereotactic body radiation therapy (SBRT). sEVs were isolated from plasma at baseline, after neoadjuvant chemotherapy, and following SBRT, and were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), nano-flow cytometry, and real-time PCR (RT-PCR). Results: The isolated sEVs exhibited an average size of <200 nm, expressed canonical exosome markers (CD63 and CD9), and exhibited pancreatic cancer (PanC)-associated markers, including cholecystokinin A receptor (CCK-AR) and carbohydrate antigen 19-9 (CA19-9). The sEV cargo included several PanC-associated microRNAs (miRNAs). Notably, the expression profiles of these miRNAs demonstrated interpatient variability, though a subset of miRNAs showed statistically significant changes following treatment. Conclusions: These findings support the feasibility of sEV isolation and molecular profiling from patient plasma and warrant further investigation as a potential source of biomarkers in pancreatic cancer.

PMID 42279288
阅读全文 →

注册免费账户还可查看另外 9996 篇文献

免费注册查看全部文献 →

了解更多fluorouracil