Drug Database
FL

fluorouracil (Carac, microsponge)

✓ Approved

Heron Therapeutics, Inc. · TYMS · Small Molecule

What is fluorouracil?

fluorouracil is a small molecule developed by Heron Therapeutics, Inc.. It is approved for therapeutic indications via transdermal.

Drug Profile

Brand NamesCarac, microsponge
CompanyHeron Therapeutics, Inc.
Drug ClassSmall Molecule
Molecular TargetTYMS
RouteTransdermal
StatusApproved
Sources: ClinicalTrials.gov, Heron Therapeutics, Inc.

Mechanism of Action

Molecular Targets

fluorouracil acts on 1 molecular target:

TYMSthymidylate synthetase (DKCD, TMS)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

fluorouracil is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Skin and subcutaneous tissue disordersActinic keratosis✓ Approved

Related Research Articles

PubMedFrontiers in immunology2026-09-19

Chronic hepatitis B and perioperative chemotherapy efficacy in colorectal liver metastases: an exploratory analysis of clinical and mechanistic evidence.

Cheng Chun-Liang CL, Tong Shan-You SY, Mo Shao-Bo SB, Cai San-Jun SJ et al.

The optimal choice of chemotherapy regimen for resectable colorectal liver metastases (CRLM) is still undetermined. The study aimed to estimate the impact of perioperative or adjuvant chemotherapy on disease-free survival (DFS), and explore the underlying mechanisms which influence chemotherapy efficacy. Eight hundred twenty-two patients undergoing curative resection of CRLM were retrospectively collected from May 2018 to December 2023. Treatment effects between perioperative and adjuvant chemotherapy were compared in full subgroup analyses by Kaplan-Meier and Cox proportional hazards methods. Single-cell RNA sequencing and tumor derived organoids were used to explore the molecular mechanisms. After propensity score matching, 630 patients were enrolled with ratio 1:1 in adjuvant and perioperative chemotherapy group. The median DFS in adjuvant and perioperative group was comparable with 28 and 32.5 months, respectively (HR = 0.99, P = 0.945). Perioperative chemotherapy was associated with improved DFS (25 vs. 13 months, P = 0.039) in patients with a clinical risk score (CRS) of 5. Notably, within the high-risk CRS 4-5 population receiving perioperative chemotherapy, patients with chronic hepatitis B (CHB) had significantly worse DFS (HR = 4.31, 95% CI 1.93-9.64; P < 0.001). Single-cell analyses revealed TSPAN8+ stem-like epithelial cells were enriched in sample with CHB. TSPAN8 knockdown sensitized colorectal cancer cells to 5-fluorouracil, and anti-TSPAN8 antibody showed synergistic efficacy with 5-fluorouracil in patient-derived liver metastasis organoids. In addition, the enhanced SPP1-CD44 signaling between TSPAN8+ epithelial cells and SPP1+ macrophages also contributed to 5-fluorouracil resistance. Higher CRS identify a subgroup of CRLM patients who may derive greater benefit from perioperative chemotherapy. HBV-related serological profiles is a potential predictor of chemotherapy resistance. The exploratory findings warrants further validation.

PMID 42761260
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PubMedMacromolecular bioscience2026-09-19

Targeting LGALS1 via CAF-Derived Extracellular Vesicles Synergizes With αPD-1 to Reverse Immunosuppression and Sensibilize Chemo-Immunotherapy for Colorectal Cancer.

Chen Sijia S, Wang Lishan L, Su Linzhe L, Zhang Luyao L et al.

Colorectal cancer (CRC) exhibits intrinsic resistance to conventional therapeutic regimens. By integrating single-cell and bulk transcriptomic data from CRC cohorts, we demonstrate that proliferative capacity alone constitutes an inadequate prognostic predictor. Instead, an immunosuppressive tumor microenvironment (TME) emerges as the dominant driver of disease progression. Galectin-1 (LGALS1), highly upregulated in metastatic CRC, correlates with robust infiltration of regulatory T cells (Tregs) and M2 macrophages to facilitate immune evasion and poor clinical outcomes, thereby serving as a promising therapeutic target for anti-tumor immunotherapy. The stromal barrier mediated by cancer-associated fibroblasts (CAFs) restricts intratumoral penetration of antitumor agents and diminishes therapeutic efficacy. To overcome this physical barrier, we constructed a CAF extracellular vesicle-based co-delivery platform termed CEV@Comb, encapsulating the LGALS1 inhibitor OTX008 and 5-fluorouracil (5-FU). CEV@Comb selectively accumulates in tumors, suppresses growth in vitro and in vivo, and remodels the immunosuppressive TME by boosting M1 macrophages and cytotoxic CD8+ T cells while reducing intratumoral Tregs. Combination therapy with CEV@Comb and anti‑programmed death‑1 antibody (αPD-1) further amplifies anti-tumor immunity in the Apc-/-, KrasG12D, Trp53-/-, Smad4-/-(AKPS) CRC mouse model. This study identifies LGALS1 as a core immunosuppressive mediator and provides an innovative chemoimmunotherapeutic strategy to improve clinical outcomes for patients with advanced CRC.

PMID 42762518
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PubMedJournal of controlled release : official journal of the Controlled Release Society2026-09-19

Mechanically adaptive dual-crosslinked hydrogel integrated with metal-phenolic cell backpacks for active keloid therapy.

Wang Shuangqing S, Huang Shiqi S, Jin Jingyu J, Zhao Jinyu J et al.

Keloids are invasive, highly recurrent fibroproliferative disorders. Clinical samples reveal a pathological pattern characterized by dysregulated extracellular matrix (ECM) remodeling, reduced NK-cell infiltration, and elevated TGF-β1. Current monotherapies have limited efficacy, and local delivery systems fail to achieve deep penetration and sustained effects due to the dense ECM barrier. To address these, we propose an active strategy of mechanically adaptive carrier delivering functionalized immune cells and develop a pH-responsive dual-crosslinked hydrogel (OR-Mg@NK@Gel) with oxyresveratrol‑magnesium (OR-Mg) metal-phenolic cell backpacks. The hydrogel is fabricated from methacrylated oxidized hyaluronic acid and 8-arm polyethylene glycol amine via sequential crosslinking of dynamic Schiff base and blue light-induced covalent networks, tuning the storage modulus to ~400 Pa to provide a soft, cell-compatible matrix with appropriate injectability and structural stability. It has interconnected macropores and pH-responsive degradation, supporting cells and enabling spatiotemporally controlled co-release of cells and therapeutics, overcoming compliance mismatch and drug burst release of conventional hydrogels. OR-Mg@NK cell backpacks are constructed by electrostatically associating surface-charge-reversed OR-Mg nanoparticles predominantly with NK cell membranes. This non-covalent modification preserves cell viability while enhancing NK cell chemotaxis via PI3K/AKT activation, enabling active penetration through dense collagen barriers. By combining hydrogel-mediated local retention with NK-cell-mediated active migration, OR-Mg@NK@Gel enables enhanced penetration through the dense ECM barrier and broader intralesional distribution. In a nude mouse keloid model, it achieved 90.62% volume inhibition and 94.26% weight inhibition, both significantly outperforming 5-fluorouracil. It also improved disordered collagen arrangement and remodeled immune microenvironment toward an anti-fibrotic state. This work provides a novel paradigm for designing efficient cell delivery systems targeting dense fibrotic tissues and holds promising translational potential.

PMID 42762840
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PubMedEuropean journal of drug metabolism and pharmacokinetics2026-09-19

Metabolic Alterations in Blood and Saliva During the First Two Cycles of Adjuvant Chemotherapy Correlate with 5-FU Dose Reduction Requirement in Patients with Colorectal Cancer.

Carlsson Göran G, Odin Elisabeth E, Gustavsson Bengt B, Wettergren Yvonne Y

Personalized therapy strategies based on patient characteristics and informative biomarkers may reduce the risk of chemotherapy-related toxicity. The aim of study was to identify changes in plasma homocysteine (HCy), 5-methyltetrahydrofolate (MTHF), pyridoxal phosphate (PLP), 5-fluorouracil (5-FU), fluorodeoxyuridine (FdUr), and deoxyuridine (dUr) levels, as well as salivary levels of uracil (Ura) and dihydrouracil (UH2) in patients with colorectal cancer (CRC) during adjuvant 5-FU-based chemotherapy. Further, the aim was to evaluate whether these metabolites have the potential to be utilized as risk markers for chemotherapy-related toxicity. Blood and saliva samples were collected from 24 patients immediately before treatment initiation on days 1 and 2 of cycle 1 (C1-1, C1-2) and cycle 2 (C2-1, C2-2). Additional blood samples were collected 10 and 30 min after 5-FU administration to enable calculation of area under the curve (AUC) values. HCy levels were determined by the chemiluminescent microparticle enzyme immunoassay method, Ura and UH2 levels by HPLC, and MTHF, PLP, 5-FU, FdUr, and dUr levels by LC-MS/MS. Significant shifts in metabolite profiles were observed across both chemotherapy cycles, with most metabolites failing to return to baseline levels between cycles. HCy levels declined progressively, whereas MTHF, PLP, FdUr, and dUr increased. Men had higher HCy levels than women. HCy levels correlated positively with age in women at baseline (r = 0.65, p = 0.029), a relationship not seen in men. HCy also correlated positively with the interval between surgery and initiation of chemotherapy during Cycle 1 (r = 0.60, p = 0.0024 at C1-2). Plasma 5-FU rose at C1-2 in both sexes but diverged during Cycle 2, decreasing in men while continuing to rise in women. Twelve patients required 5-FU dose reduction. These patients had higher plasma HCy and lower salivary Ura at C1-1 and C2-1, along with greater increases in Ura and 5-FU between C2-2 and C1-2 (Δ-values). A predictive model incorporating ΔUra, Δ5-FU, and sex strongly predicted need for 5-FU dose reduction (p < 0.0001). Significant alterations in metabolite levels occur during the first two cycles of adjuvant 5-FU-based chemotherapy, potentially contributing to treatment-related toxicity. Moderate associations between HCy levels, patient age, and timing of chemotherapy initiation suggest that patient-related factors may influence one-carbon metabolism during 5-FU/LV therapy. Higher Ura and 5-FU levels in women during Cycle 2 may contribute to sex-related differences in treatment-related toxicity. Changes in Ura and 5-FU levels between treatment cycles (ΔUra and Δ5-FU AUC) might be particularly informative for guiding individualized 5-FU dose adjustments, especially when interpreted in the context of patient sex.

PMID 42762271
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PubMedCase reports in cardiology2026-09-18

5-Fluorouracil (5-FU) Cardiotoxicity: A Stressful Event.

Desai Yash Y, Singh Rohan R, Desai Kush K, Bennett Samuel S et al.

5-Fluorouracil (5-FU), a chemotherapeutic agent, is routinely used for solid tumors. Known cardiotoxic effects of 5-FU include fatal arrhythmias, myocardial infarctions, and coronary vasospasms. This case report describes a 56-year-old man who had acute heart failure with cardiogenic shock suspected to be related to 5-FU exposure; notably, cardiac dysfunction resolved following cessation of therapy.

PMID 42756395
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PubMedCancer chemotherapy and pharmacology2026-09-17

Risk factors associated with febrile neutropenia in patients with esophageal cancer receiving 5-fluorouracil plus cisplatin combination chemoradiotherapy.

Eto Daiki D, Shiraiwa Ken K, Tanaka Ryota R, Sumimoto Takahiro T et al.

To identify risk factors for febrile neutropenia (FN) in patients with esophageal cancer receiving the first cycle of definitive chemoradiotherapy with 5-fluorouracil plus cisplatin and concurrent radiotherapy (FP+R therapy). We conducted a retrospective single-center cohort study of patients who started FP+R at Oita University Hospital between April 2011 and June 2023. The primary outcome was FN onset in cycle 1. Univariate tests and multivariable logistic regression [forced entry: age, C-reactive protein (CRP), prognostic nutritional index (PNI), dysphagia] were used to evaluate association with FN development. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive performance of baseline CRP for FN. Among 120 patients studied, grade ≥ 3 neutropenia occurred in 37 (30.8%) and FN in 14 (11.7%) during the first cycle. In multivariable analysis, higher baseline CRP was independently associated with increased FN risk [odds ratio (OR) 1.790; 95% confidence interval (CI) 1.120-2.850; p = 0.014], whereas dysphagia showed a non-significant association (OR 2.890; p = 0.145). Age and PNI were not independent predictors. ROC analysis for baseline CRP yielded area under the ROC curve of 0.699 (95% CI 0.520-0.877; p = 0.021) with optimal cut-off value of 0.68 mg/dL (sensitivity 61.54%; specificity 70.65%). Baseline systemic inflammation, indicated by elevated CRP, is an independent risk factor for FN development during FP+R therapy. Despite the regimen having an intermediate FN risk, patients with elevated pre-treatment CRP may need closer monitoring. This biomarker may help clinicians perform a more comprehensive risk assessment alongside conventional patient-specific factors.

PMID 42752673
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