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

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

PubMedDiscover nano2026-07-17

Green synthesized cobalt doped graphene quantum dots derived from Boswellia serrata for dual ligand targeted bioimaging and delivery of exemestane.

Harde Minal T MT, Ingle Rahul R, Dhamal Sakshi S, Deshmukh Prashant P et al.

Major objective of hydrothermal method is to achieve the synthesis of Cobalt doped Graphene quantum dots (Co-GQDs) using natural precursor (Boswellia serrata gum resin). The Co-GQDs were surface engineered with folic acid (FA) and hyaluronic acid (HA) to enable dual targeting module (Co-GQDFH), followed by loading of the anticancer drug Exemestane (EXE@Co-GQDs). The nanosized, crystallite structure with high luminescence intensity was maintained after functionalization and drug loading process was assessed from preliminary physicochemical analysis. The EXE@Co-GQDFH forms complex via passive loading approach and achieves and entrapment efficiency of 68.58%. The in-vitro drug release study shows extended release of EXE from the surface functionalized Co-GQDFH for 24 h and releases (~ 88%) maximum encapsulated drug. The dose dependent toxicity was observed for EXE@Co-GQDFH (49.5 µg/ml) on MCF-7 cell breast cancer cell types while IC50 value was comparable to 5-Fluorouracil. The fluorescent Co-GQD shows high bioimaging and cellular uptake efficiency in MCF-7 cells. The surface conjugation with FA and HA on Co-GQDs shows enhanced activity with zone of inhibition was found to be 25 mm while the Co-GQD shows 20 mm suggest conjugation improved the antimicrobial effect. Radical scavenging activity was also demonstrated, with Co-GQDs showing 77.92% and EXE@Co-GQDs was 59.02% DPPH inhibition. These results suggest that surface-engineered Co-GQDs offer a multidentate nanoplatform for targeted delivery, imaging, and therapy in breast cancer applications.

PubMedLangenbeck's archives of surgery2026-07-17

A comparative evaluation of the GINI index and the modified Glasgow prognostic score in predicting postoperative sarcopenia in rectal cancer patients undergoing NACRT.

Yener Mehmet Kemal MK, Kılavuz Hüseyin H, Bilir Burak B, Gökçe Ayşe A et al.

Postoperative sarcopenia following neoadjuvant chemoradiotherapy for locally advanced rectal cancer negatively affects recovery and oncological outcomes. Both the Global Immune Nutrition and Inflammation Index (GINI) and the modified Glasgow Prognostic Score (mGPS) are derived from routine laboratory data. There are no studies comparing the performance of these scores and indices in predicting sarcopenia in patients with CT-confirmed sarcopenia. The aim of this study is to determine which of these two indices is a more specific predictor of postoperative sarcopenia in patients who underwent surgery after NACRT in this patient population. This single-center retrospective cohort study (January 2019-December 2025) included 134 adults with locally advanced rectal adenocarcinoma who underwent total mesorectal excision after completing standard 5-fluorouracil/leucovorin/oxaliplatin-based neoadjuvant chemoradiotherapy (NACRT). GINI and mGPS values were calculated from fasting blood samples collected one month after NACRT. Postoperative sarcopenia was defined using gender-specific skeletal muscle index (SMI) cutoff values at the level of the third lumbar vertebra, as determined by CT scans performed three to six months after surgery. The prevalence of postoperative sarcopenia was 30.6% (41/134). Sarcopenic patients had lower albumin levels (35.76 vs. 38.07 g/L; p = 0.046) and higher GINI values (median 146.70 vs. 68.39; p = 0.018); there was no difference between mGPS categories (p = 0.558). The GINI index yielded an AUC value of 0.629 (95% CI 0.541-0.711; sensitivity 48.78%, specificity 79.57% when the cutoff value was > 156.25; Nagelkerke R² = 0.140), whereas mGPS showed no discriminatory power (AUC 0.551; p = 0.307). In the adjusted analysis, a high GINI value independently predicted sarcopenia (aOR 4.93, 95% CI 1.72-14.13; p = 0.003). In patients with locally advanced rectal cancer, a high GINI value after NACRT was independently associated with sarcopenia assessed by postoperative CT, whereas no such association was found with mGPS. Moderate discriminatory performance and a wide 95% confidence interval indicate that the GINI, in its current form, is insufficient as a standalone clinical decision-making tool; therefore, these findings should be considered hypothesis-generating and must be supported by a prospective, multicenter validation study before being implemented in clinical practice.

PubMedChinese medicine2026-07-17

Guiqi Baizhu prescription attenuates 5-FU-induced intestinal mucositis by targeting IKKβ to inhibit M1 macrophage polarization.

Zhou Yu-Cen YC, Li Ya-Ling YL, Ma Jing J, Li Junjie J et al.

Chemotherapy-induced intestinal mucositis (CIM), particularly that induced by agents such as 5-fluorouracil (5-FU), frequently leads to chemotherapy discontinuation. However, effective treatment options remain limited. Guiqi Baizhu prescription (GQBZP), a traditional Chinese medicine formula, has been reported to possess anticancer, analgesic, and anti-inflammatory activities. This study aimed to evaluate the therapeutic efficacy of GQBZP against 5-FU-induced intestinal mucositis (IM) and to clarify its underlying molecular mechanisms and material basis. The protective effects and mechanistic actions of GQBZP were investigated using a murine model of 5-FU-induced IM. Potential IKKβ-targeting compounds within GQBZP were screened through virtual docking combined with CCK-8 assays and subsequently evaluated in 5-FU-stimulated human intestinal epithelial cells (HIECs) and lipopolysaccharide/interferon-γ (LPS/IFN-γ)-stimulated THP-1 macrophages. Target specificity and binding characteristics were further validated by molecular dynamics (MD) simulations, surface plasmon resonance (SPR) analysis, and experiments using IKKβ-overexpressing HEK293T cells. In vivo experiments demonstrated that GQBZP significantly alleviated 5-FU-induced IM by suppressing M1 macrophage polarization within intestinal tissues and restoring intestinal barrier integrity, effects closely associated with modulation of the IKKβ/NF-κB signaling pathway. Virtual screening and CCK-8 assays identified five IKKβ-targeting compounds in GQBZP: Rhamnocitrin, Toralactone, Naringenin, Liquiritigenin, and Carvacrol. These compounds markedly reduced apoptosis and pro-inflammatory cytokine production in 5-FU-treated HIECs. In addition, they inhibited M1 macrophage polarization and cytokine release in LPS/IFN-γ-stimulated THP-1 cells, accompanied by attenuation of IKKβ/NF-κB pathway activation. MD simulations, SPR assays, and functional studies in IKKβ-overexpressing HEK293T cells further confirmed that Toralactone directly binds to and suppresses IKKβ activation, whereas Rhamnocitrin modulates IKKβ activity through an indirect regulatory mechanism. GQBZP alleviates 5-FU-induced IM by promoting recovery of the intestinal epithelial barrier and inhibiting M1 macrophage polarization through an IKKβ/NF-κB-dependent mechanism, thereby exerting synergistic anti-inflammatory effects. Toralactone was identified as a key active constituent responsible for direct inhibition of IKKβ-mediated M1 polarization. These findings suggest that targeting IKKβ to regulate macrophage polarization represents a promising therapeutic strategy for the management of CIM.

PubMedExpert opinion on therapeutic targets2026-07-17

5-FU in combination with PARP inhibitor ABT-888 deregulates MGMT-dependent mismatch repair (MMR) pathway in MMR-proficient colorectal cancer stem cells by modulating MGMT/PARP1/MSH6 complex.

Paul Subarno S, Das Chinmay C, Bhal Subhasmita S, Sinha Saptarshi S et al.

Previous study showed the PARP inhibitor ABT-888 potentiates the cytotoxicity of 5-fluorouracil (5-FU) by inhibiting PARP1-mediated mismatch repair (MMR) pathway via MSH6 deregulation in MMR-proficient colorectal cancer stem cells (CRC-CSCs). Emerging evidence indicates 5-FU regulates O6 -methylguanine-DNA-methyltransferase (MGMT) activity, but the mechanistic basis of MGMT involvement in PARP1-mediated MMR pathway following 5-FU treatment remains complex and poorly defined. This study delineates the role of MGMT in 5-FU-induced MMR pathway activation and evaluates 5-FU+ABT-888 combination effects on MGMT modulation in CRC-CSCs. The molecular mechanism has been studied by using colocalization, western blot, co-immunoprecipitation, MGMT gene-knockdown, and molecular docking in in vitro, in silico, and ex vivo preclinical models. 5-FU treatment induced PARylated-PARP1 in CRC-CSCs, promoting PARP1-MGMT-MSH6 interactions that activated MMR. ABT-888 inhibited PARylation in 5-FU-pre-exposed CSCs. Therefore, PARP1 could not physically interact with both MGMT and MSH6, and complete abolishment of MGMT and MSH6, and MMR protein downregulation were observed in combination treatment. MGMT silencing confirmed its critical role in PARP1-mediated MMR activation. Similar findings were obtained in in silico and ex vivo models. 5-FU+ABT-888 enhanced CRC-CSCs death by inhibiting the PARP1-MGMT-MSH6 interaction and simultaneously inhibiting the MGMT-dependent PARP1-mediated MMR pathway in MMR-proficient CRC-CSCs.Schematic model illustrating 5-FU and ABT-888 combination treatment induces apoptosis by inhibiting the MGMT-dependent MMR pathway in CRC-CSCs. The diagram proposes a mechanistic link between PARP1, MGMT, and MMR signaling in regulating 5-FU response and PARP-inhibitor-mediated cytotoxicity in MMR-proficient CRC-CSCs. Left panel (Cancer survival): (1) 5-FU is incorporated into DNA, generating 5-FU-induced DNA adducts in MMR-proficient CRC-CSCs. (2) PARP1 is recruited to damaged DNA and (3) becomes activated, leading to PARylation. (4) MGMT acts as a PAR acceptor and binds activated PARP1 at sites of damage. (5) MSH6, together with MSH2 (MutSα), serves as an additional PAR acceptor and associates with PARylated PARP1 and MGMT, promoting recruitment of downstream MMR heterodimers. (6) The MutL complex (MLH1-PMS2) is subsequently recruited to the mismatch site, forming a multi-protein repair complex with PARP1, MGMT, MSH2, and MSH6. (7) This cascade enables efficient MMR processing and pathway activation, thereby sustaining survival of MMR-proficient CRC-CSCs. Right panel (Cancer reduction): (8) Upon treatment with the PARP inhibitor ABT-888, PARP1-PARylation is blocked. (9) Consequently, MGMT and MSH6 fail to interact with PARP1, preventing further recruitment of MMR components and leading to defective MGMT-dependent MMR signaling in 5-FU pre-exposed CRC-CSCs, ultimately triggering apoptosis and reducing the cancer stem cell population. Created in BioRender (https://biorender.com/i29644a).

PubMedBioorganic chemistry2026-07-16

5-Fluorouracil loaded copper‑aluminum layered double hydroxides inhibit colorectal cancer cells by inducing oxidative stress, mitochondrial membrane depolarization, apoptosis, and cell cycle arrest.

Yin Ying Y, Shi Jiayan J, Lu Dingyi D, Wang Yueran Y et al.

Colorectal cancer (CRC) is one of the global health issues. Current treatments still present major challenges such as off-target cytotoxicity and the emergence of drug resistance, the development of potent and innovative therapeutics is urgently needed. Here, we synthesized copper‑aluminum (CuAl) layered double hydroxides (LDH) using a hydrothermal method and loaded them with the 5-fluorouracil (5-FU) (CuAl-5FU) to improve their anticancer efficacy. The LDHs were 2D-sheeted and rosette-like in shape. The hydrodynamic diameter of CuAl and CuAl-5FU was 568 and 661 nm, respectively. Zeta potential values of CuAl-5FU ranged from +31.39 to +34.93 mV across pH 3 to 9, indicating good colloidal stability. The drug loading and encapsulation efficiency were 18.19% and 36.37%, respectively. Dose-dependent cytotoxicity was seen in HCT-116 and HT-29 CRC cells. Comparatively, CuAl-5FU LDH exhibited greater anticancer activity compared to LDH alone and free 5-FU drug in both monolayer and tumor spheroid models. Mechanistic studies revealed that CuAl-5FU significantly induced reactive oxygen species (ROS) production, mitochondrial membrane depolarization, and promoted apoptosis by upregulating the pro-apoptotic Bax protein and PARP cleavage in both CRC cells. Transcriptomic analysis and qPCR validation revealed the downregulation of oncogenic MAPK signaling and modulation of key genes related to proliferation (JUN, DUSP1, FOSB, EGR1, and FOS), apoptosis (TP53I3, ZMAT3, GADD45A, BBC3, MDM2, TNFRSF10B, E2F1, and ORC1), and cell cycle arrest (CDKN1A and CDC25A). Notably, we identified altered expression of several chemoresistance-related genes (AVPI1, HROB, DDIAS, PTGES, and LAMA3), suggesting the early emergence of adaptive responses in CRC cells. To validate this observation, CuAl-5FU-resistant HCT-116 G3 and HT-29 G2 cell lines were established and their chemoresistant phenotypes were characterized. Indeed, the chemoresistance-associated genes were upregulated, together with significantly higher IC50 values and clonogenic survival fractions than their respective parental cells. Collectively, these findings suggest that CuAl-5FU improves anticancer activity in CRC cells by modulating multiple genes involved in ROS production, mitochondrial membrane depolarization, apoptosis, and cell cycle regulation. Nevertheless, chemoresistance developed rapidly following repeated treatment, highlighting a potential limitation of this therapeutic approach. Overall, this study provides a new potential strategy for CRC treatment while emphasizing the importance of elucidating the molecular mechanisms underlying acquired chemoresistance. Future studies should also optimize the physicochemical properties of the CuAl-5FU LDH, particularly the large particle size (∼661 nm) by optimizing the hydrothermal synthesis conditions and incorporating surface modifications to further improve the tumor penetration and drug delivery.

PubMedBiomedical optics express2026-07-16

Longitudinal drug response assessment of tumor organoids based on optical attenuation coefficient and multi-dimensional morphological characterization.

Yang Shanshan S, Guo Jing J, Wang Wanli W, Feng Zhe Z et al.

Patient-derived tumor organoids (PDTOs) are vital for precision oncology, but standard drug screening methods, including adenosine triphosphate (ATP) assays, are destructive and prevent longitudinal monitoring. Optical coherence tomography (OCT) offers non-destructive 3D imaging, capturing morphological features and tissue attenuation characteristics via the optical attenuation coefficient (OAC). Here, we propose a non-destructive evaluation framework for tumor organoids that fuses OAC and multi-dimensional morphological features. Using intrahepatic cholangiocarcinoma (iCCA) PDTOs treated with icaritin, we found that OAC exhibited a significant dose-dependent increase (up to 32.8% at 80 μM compared to control), accompanied by a morphological transition of cystic organoids into solid phenotypes. By integrating these features via K-means++ clustering and principal component analysis, we constructed a relative growth score. This fusion score correlated strongly with the ATP gold standard (Pearson correlation coefficient r = 0.938), outperforming a morphology-only model (r = 0.906). Furthermore, independent experiments with first-line chemotherapeutics (e.g., 5-Fluorouracil, Gemcitabine) and combinatorial regimens indicated the model's potential generalizability (r = 0.887). This method overcomes the limitations of destructive, single-metric evaluations, providing a quantitative and non-destructive platform for high-throughput drug screening and personalized treatment decision-making.

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