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更新于：2026-08-27

Fluorouracil

氟尿嘧啶

更新于：2026-08-27

概要

基本信息

药物类型

小分子化药

别名

5-fluoro-1H-pyrimidine-2,4-dione、5-Fluoropyrimidine-2,4-dione、5-Fluorouracil

+ [38]

靶点

TYMS

作用方式

抑制剂

作用机制

TYMS抑制剂(胸苷酸合成酶抑制剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [10]

在研适应症

胰腺腺癌胃腺癌食管癌+ [93]

非在研适应症

腺泡细胞癌胆道腺癌转移性腺癌+ [120]

原研机构

Spectrum Pharmaceuticals, Inc.

在研机构

Lineberger Comprehensive Cancer Center

National Cancer Institute

NRG Oncology

+ [24]

非在研机构

Wake Forest School of Medicine

The Cleveland Clinic Foundation

Mayo Clinic

+ [49]

权益机构

Dr. Reddy's Laboratories Ltd.

Hill Dermaceuticals, Inc.

Extrovis AG

+ [1]

最高研发阶段批准上市

首次获批日期

美国 (1962-04-25),

乳腺癌结直肠癌胰腺癌+ [1]

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)

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结构/序列

分子式C4H3FN2O2

InChIKeyGHASVSINZRGABV-UHFFFAOYSA-N

CAS号51-21-8

关联

3,010

项与氟尿嘧啶相关的临床试验

NCT07748611

/ Not yet recruiting临床2期IIT

SMART-PANC: SMAD4 Tailored Neoadjuvant Therapy for Pancreatic Cancer, A Phase ll Non-Randomized, Single Center Pilot Study

This phase II trial tests the impact of using SMAD4-mutant status to personalize chemotherapy in treating patients with pancreatic ductal adenocarcinoma (PDAC) that can be removed by surgery (resectable) or that may be between resectable and unresectable (borderline resectable) before undergoing surgery (neoadjuvant). PDAC is one of the most aggressive and fastest growing tumors. SMAD4, a tumor suppressor gene, acts like a brake on cell growth and helps to prevent tumor cells from growing. However, losing it makes the tumor more aggressive and often resistant to standard of care (SOC) treatments regimens, such as gemcitabine with nab-paclitaxel and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic (DNA) and may kill tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Fluorouracil, a type of antimetabolite, stops cells from making DNA and it may kill tumor cells. Leucovorin is a form of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Instead of a one-sized fits all treatment approach with SOC therapies, matching therapy based on SMAD4 mutation status may use this specific genetic weakness against the tumor. This approach to neoadjuvant therapy may dramatically alter the path of treatment and improve outcomes, including complete resection rates, in patients with resectable or borderline resectable PDAC.

开始日期2027-02-03

申办/合作机构

Northwestern University

[+1]

NCT07271355

/ Not yet recruiting临床3期IIT

Investigation of Mitomycin C PIPAC - FOLFIRI Combination for Unresectable Appendiceal or Colorectal Peritoneal Metastases Treatment (IMPACT): A Multicenter, Randomized, Open-Label, Phase 3 Trial

This phase III trial studies how well pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin works versus (vs) standard chemotherapy (leucovorin calcium, fluorouracil, and irinotecan hydrochloride [FOLFIRI regimen] plus bevacizumab) in treating patients with appendix or colorectal cancer that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to the abdominal cavity (peritoneal metastases). PIPAC is a new therapeutic approach that is minimally invasive, does not require surgery (laparotomy), and can be frequently repeated. Chemotherapy is delivered as a pressurized mist directly inside the abdominal cavity (peritoneum) during a minimally invasive surgery called a laparoscopy. The pressure helps the chemotherapy absorb into the cancer tissue and spread more evenly. Mitomycin is an antibiotic used as a chemotherapy drug. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their deoxyribonucleic acid (DNA). Standard chemotherapy drugs, such as those in the FOLFIRI regimen, are given via infusion into a vein (intravenously), and work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Another standard intravenous drug, bevacizumab, is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving mitomycin via PIPAC in combination with the standard FOLFIRI regimen, with or without bevacizumab, may work better than standard FOLFIRI plus bevacizumab alone in treating patients with unresectable appendix or colorectal cancer with peritoneal metastases.

开始日期2026-10-01

申办/合作机构

City of Hope National Medical Center

[+1]

NCT07775287

/ Recruiting临床3期

A Randomized, Open-label, Phase 3 Trial of Petosemtamab + FOLFIRI/mFOLFOX6 Versus Cetuximab or Bevacizumab + FOLFIRI/mFOLFOX6 as Second-line Treatment in Participants With RAS and BRAF Wild-type, Recurrent, Unresectable or Metastatic Colorectal Cancer

The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and that cannot be safely removed by surgery or has spread to other parts of the body.
Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo.
The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open.
Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective.
The overall study duration (including screening, treatment, and follow-up) will be different for every participant.

开始日期2026-09-15

申办/合作机构

Genmab A/S

100 项与氟尿嘧啶相关的临床结果

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100 项与氟尿嘧啶相关的转化医学

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100 项与氟尿嘧啶相关的专利（医药）

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62,171

项与氟尿嘧啶相关的文献（医药）

2027-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Phytochemical basis and mechanistic insight of Swertia macrosperma in treating 5-fluorouracil-induced diarrhea

Article

作者: Ruan, Jingya ; Wang, Tao ; Yan, Wenjia ; Zhang, Yi ; Li, Huimin ; Cheng, Jiaming ; Geng, Qianqian ; Wu, Yijin ; Li, Fei ; Cao, Xiaoyan

ETHNOPHARMACOLOGICAL RELEVANCE:

5-Fluorouracil (5-FU)-induced diarrhea severely impacts chemotherapy outcomes. Swertia macrosperma (C. B. Clarke) C. B. Clarke in Hook. f. is traditionally used for diarrhea, yet its efficacy and mechanism remain unclear.

AIM OF THE STUDY:

This study first investigated the anti-diarrheal potential of 70% ethanol extract from S. macrosperma (SME).

MATERIALS AND METHODS:

In a 5-FU-induced mouse model, SME was evaluated for its effects on diarrhea severity, weight loss, intestinal histopathology, oxidative stress (MDA, SOD, GSH), inflammation (TNF-α, IL-6, COX-2, iNOS), and tight junction proteins (Claudin-1, Occludin). Phytochemical investigation (including isolation, structural elucidation, and UPLC-MS quantification), IEC-6 cell-based mechanistic studies, network pharmacology, and Western blot analysis (for PI3K-AKT pathway) were performed.

RESULTS:

SME significantly alleviated weight loss, diarrhea severity, and intestinal histopathological damage. It inhibited oxidative stress and inflammation while upregulating tight junction proteins, thereby protecting intestinal barrier integrity. Phytochemical investigation yielded 57 compounds, including three new isolates (swemacronosides A-C) and 37 first-time reports for this species. UPLC-MS quantification identified compounds 7, 8, and 23 as the predominant constituents. Mechanistic studies indicated that SME ameliorated diarrhea symptoms in mice via the PI3K-AKT signaling pathway. Western blot confirmed that compounds 7 and 23 significantly restored the 5-FU-induced downregulation of PI3K expression and the p-AKT/AKT ratio.

CONCLUSION:

S. macrosperma ameliorates 5-FU-induced diarrhea, and the mechanism potentially involves the PI3K-AKT pathway. However, under the present experimental conditions, it did not significantly reverse 5-FU-induced thymic and splenic atrophy. These findings provide a scientific basis for clinical application and offer potential chemical markers for future quality control studies of S. macrosperma.

2026-12-31·Gut microbes reports

Comparative preventive effects of probiotic and postbiotic preparations of Lacticaseibacillus rhamnosus L156.4 and GG in a 5-FU-induced mucositis model

Article

作者: Figueiredo Siqueira, Milca da Silva ; Pires, Luiz Octávio ; Elias Moreira Júnior, Renato ; Cardoso, Valbert Nascimento ; Freitas, Andria dos Santos ; Guimarães Sousa, Eduarda ; Lima Barroso, Fernanda Alvarenga ; Souza, Renan Pedra de ; Antunes Fernandes, Simone Odília ; Munis Campos, Gabriela ; Ferrary Américo, Monique ; Viegas Santos, Rhayane Cristina ; Santos, Tulio Marcos ; Brunialti Godard, Ana Lucia ; Azevedo, Vasco ; Silva Quaresma, Ludmila ; Carvalho, Rodrigo Dias de Oliveira ; Gomes, Gabriel Camargos ; Guédon, Eric ; Lima de Jesus, Luís Claúdio ; Ferreira, Enio ; Canário Viana, Marcus Vinícios ; Le Loir, Yves

Intestinal mucositis is a debilitating side effect of chemotherapy, characterized by epithelial damage, inflammation, and microbial dysbiosis, that significantly impairs patients' quality of life. This study evaluated the therapeutic potential of Lacticaseibacillus rhamnosus L156.4 in its live, heat-inactivated, and supernatant forms, compared to the reference strain L. rhamnosus GG (LGG), in a murine model of 5-fluorouracil (5-FU)-induced mucositis. Preventive treatment with live L156.4 significantly reduced mucositis-induced intestinal damage, preserving villus length, crypt depth, and goblet cell numbers, thereby supporting barrier integrity. In contrast, heat-inactivated and supernatant forms provided only limited protection. Both live L156.4 and LGG reduced myeloperoxidase activity and downregulated inflammatory markers such as Il1b and Nfkb1, confirming anti-inflammatory effects. They also modulated tight junction-related gene expression with L156.4 showing strong induction of Muc2, suggesting enhanced epithelial protection. Fecal microbiota analysis showed that, whereas LGG restored the loss of bacterial diversity and evenness induced by 5-FU, L156.4 primarily modulated microbiota composition by restoring the abundance of specific phyla and genera. Overall, our findings identify L156.4 as a promising probiotic candidate, with effects comparable to and complementarity with LGG, for mitigating chemotherapy-induced mucositis. Further studies are required to assess dose effects and long-term safety.

2026-12-31·ANNALS OF MEDICINE

Comparative efficacy of intralesional therapies for keloid scars: a network meta-analysis

Review

作者: Bentley, Alexa ; Romano, Candela ; Sanchez Cruz, Camila ; Perozo, Karla ; de Araujo, William Matheus ; Calderon Martinez, Ernesto ; Medina, Jose ; Magallanes Bajana, Angelo ; Ríos, Christopher Romero ; Mohamed Khalil, Malaz El Zubair

BACKGROUND:

Keloids are pathological scars causing pain, pruritus, and emotional distress. While common treatments exist, emerging options such as insulin and botulinum toxin A (BTX-A) are underrepresented in comparative analyses. This network meta-analysis (NMA) aimed to evaluate the efficacy and safety profiles of various intralesional therapies for keloid scars.

METHODS:

A PRISMA-guided search across seven databases was conducted on July 2025 and preregistered on PROSPERO (CRD420251088758). Included studies were randomized, non-randomized, and crossover trials of intralesional therapies. Pairwise and NMA were conducted for efficacy (keloid size/volume reduction), recurrence, and safety (adverse effects). Treatment rankings were based on surface under the cumulative ranking curve (SUCRA) scores. Statistical significance was set at (p < 0.05).

RESULTS:

From 51 studies (3234 participants, 23 interventions), 5-fluorouracil (5-FU) + corticoids significantly improved keloid reduction compared to corticoids alone (RR = 1.59; 95% CI: 1.31-1.92; p < 0.01), with 5-FU + corticoids + YAG:Laser (RR = 2.73; 95% CI: 1.36-5.48; p < 0.01) showing an even greater effect. SUCRA values indicated that 5-FU + corticoids + YAG:Laser (0.95), vitamin D + platelet rich plasma (0.83), and 5-FU + corticoids (0.78) had the highest probability of effectiveness. For recurrence, no significant differences were found across interventions, suggesting insufficient evidence. Regarding adverse effects, a significant risk reduction was found for BTX-A (RR = 0.29; 95% CI: 0.09-0.95; p = 0.04) and Verapamil (RR = 0.35; 95% CI: 0.14-0.84; p = 0.01) compared to corticoids; others showed no significant effects.

CONCLUSION:

This NMA provides a comparative overview, indicating that combination therapies, most notably 5-FU + corticoids + YAG:Laser, offer the greatest benefit. While data for novel agents (insulin and BTX-A) suggest potential, further research with standardized methodologies and longer-term follow-up is crucial to define optimal treatment algorithms.

3,700

项与氟尿嘧啶相关的新闻（医药）

2026-08-27

·癌度

PD-L1 ADC+EGFR单抗/PD-1三条线布局,HLX43联合疗法向结直肠癌后线治疗发起冲击！

点击蓝字关注我们同一款PD-L1 ADC,分别搭配EGFR单抗和PD-1抑制剂,复宏汉霖想在结直肠癌里同时验证两条路能不能走通。一、一线治疗失败之后,结直肠癌患者的选择在收窄晚期或转移性结直肠癌(mCRC)的一线标准治疗通常以5-FU为基础,但大多数患者治疗一段时间后会出现疾病进展。进入二线及以后,可选方案明显减少,部分患者能用上PD-1抑制剂或靶向药,但获益人群有限、整体有效率不高。临床上确实需要新机制的治疗方案来填补这段空白。图片来自摄图网二、HLX43:一款身兼两职的PD-L1 ADC HLX43是复宏汉霖自主研发的靶向PD-L1的抗体药物偶联物,由全人源抗PD-L1抗体和拓扑异构酶I抑制剂载荷偶联而成,药物抗体比约为8。它的设计思路是"精准杀伤+免疫激活"两条腿走路: 一方面通过PD-L1抗体锁定肿瘤细胞、内吞后释放毒素直接杀伤,毒素还能借助旁观者效应波及周围不表达PD-L1的肿瘤细胞; 另一方面,PD-L1抗体本身也能激活免疫调节机制,起到协同抗肿瘤的作用。目前HLX43已经在非小细胞肺癌、宫颈癌、头颈癌、胃癌、食管癌等十余个瘤种里开展临床研究,全球入组患者超过700例,是目前全球进展较快的PD-L1 ADC之一,今年10月还因为在胸腺癌后线治疗中的初步疗效拿到了美国FDA孤儿药资格认定。已经公布的数据里,宫颈癌II期研究总人群客观缓解率41.4%、疾病控制率82.8%,其中3mg/kg剂量组ORR和DCR分别达到70.0%和100%;非小细胞肺癌方面,今年WCLC大会更新的数据显示,鳞状NSCLC后线治疗在2mg/kg剂量组ORR为40.0%、DCR为73.3%,针对多西他赛治疗失败的三线及以上患者,ORR仍能达到30.0%、DCR为80%。这些数据说明HLX43在多个瘤种里都有一定的广谱抗肿瘤活性,不过这些都是早期研究数据,样本量普遍不大,能不能在结直肠癌里复制类似效果,还需要这项新研究来验证。三、两个搭档:HLX07和斯鲁利单抗 HLX07(pimurutamab)是复宏汉霖自主研发的抗EGFR人源化单抗,相比已上市的西妥昔单抗,做了免疫原性更低、靶点亲和力更好的改良,理论上能减少输液反应和过敏风险。因为抗EGFR单抗在RAS/BRAF野生型结直肠癌里的疗效已经有比较成熟的临床证据支持,这项研究里HLX07联合组会优先纳入RAS/BRAF野生型患者。值得一提的是,HLX07联合斯鲁利单抗及化疗用于EGFR高表达鳞状NSCLC一线治疗时,中位随访18.6个月的数据显示客观缓解率约70%、疾病控制率超过90%,高剂量组中位无进展生存期达17.4个月——这是肺癌人群的数据,不能直接套用到结直肠癌上,但至少说明HLX07和斯鲁利单抗这个组合本身有一定的协同基础。斯鲁利单抗(H药汉斯状)是复宏汉霖自主研发的抗PD-1单抗,已经在国内获批多个适应症,包括一线治疗广泛期小细胞肺癌,大规模人群里的疗效和安全性已经得到验证。四、Ib/II期临床:全国多中心招募中基于这些早期信号,复宏汉霖启动了HLX43联合HLX07或斯鲁利单抗治疗晚期/转移性结直肠癌的Ib/II期研究(HLX43-mCRC202),登记号CTR20255223、海外登记号NCT07358585,计划入组126例,按1:1随机分成两组:一组是HLX43联合HLX07,优先纳入RAS/BRAF野生型患者;另一组是HLX43联合斯鲁利单抗。主要入组条件: 年龄18岁以上；经组织学或细胞学确诊为晚期或转移性结直肠腺癌的患者；以5-FU为基础的一线治疗出现影像学进展； ECOG体力状态评分0到1分；具有1厘米以上可测量病灶; HLX07联合组还需要经当地实验室检测确认为RAS/BRAF野生型。研究已在复旦大学附属肿瘤医院、中山大学肿瘤防治中心等全国多个省市的中心同步开展,患者可就近参与,具体能否入组以研究中心医生评估为准。写在最后结直肠癌一线治疗失败后的困境,正在被越来越多的新机制疗法尝试破解。HLX43这款PD-L1 ADC已经在宫颈癌、非小细胞肺癌等多个瘤种里展现出初步的广谱抗肿瘤活性,这次联合抗EGFR单抗或PD-1抑制剂进入结直肠癌领域,是把已有信号往新瘤种推进的一次尝试,具体效果如何,还是要看这项Ib/II期研究的数据说话。如果你或家人正面临一线标准治疗失败的困境,不妨对照上述入组条件了解一下这个机会。关注癌度,解读基因检测报告,评估临床试验入组机会,欢迎通过下面3个方式联系我们。 👉 点击文末【阅读原文】；或关注公众号后点菜单栏“联系我们”；或微信直接扫描下图二维码；我们协助您申请适合您的临床试验！免责声明:本文仅为科普参考,不构成任何医疗建议。HLX43、HLX07及相关联合方案均为临床研究阶段产品,尚未获批上市,文中涉及的部分疗效数据来自其他瘤种,不代表在结直肠癌中的预期疗效。所有治疗决策请在专业医生指导下进行,最终能否入组以研究医生面诊及各项筛选检查结果为准。点赞收藏分享点亮小手爱心，送来温暖鼓励

2026-08-26

·生物器材网

控制器官大小、维持组织稳态的Hippo信号通路作用机制与相关药物研发

Hippo信号通路（Hippo signal pathway）是进化高度保守的激酶信号转导通路，最早在果蝇中发现，因Hippo基因突变导致果蝇头部增大、颈部出现褶皱，形似河马而得名。核心功能是控制器官大小、维持组织稳态及参与再生修复，其功能失调会驱动肿瘤等多种疾病发生。Hippo信号通路凭借“控制器官大小、维持组织稳态”这一核心功能，成为发育生物学、肿瘤学、再生医学交叉领域的研究热点。一、Hippo信号通路的核心结构核心激酶级联：Hippo（MST1/2）→ LATS1/2，辅因子包括SAV1和MOB1[1]。转录效应因子：Yki（果蝇）/ YAP/TAZ（哺乳动物），与TEAD转录因子结合激活下游基因。 YAP/TAZ调控：LATS磷酸化YAP/TAZ，促进其胞质滞留或降解；也可通过其他激酶（如AMPK、NLK）或非磷酸化机制（如胞质隔离）调控[1]。二、Hippo通路的核心作用机制通路的活性由YAP/TAZ的亚细胞定位决定：通路激活状态（ON）：上游信号传入后，MST1/2与MAP4K家族共同磷酸化激活LATS1/2，活化的LATS1/2进一步磷酸化YAP的S127位点、TAZ的S89位点。磷酸化的YAP/TAZ与14-3-3蛋白结合，被锚定在细胞质中，后续通过泛素化途径被蛋白酶体降解，下游促增殖靶基因的转录被关闭。通路抑制状态（OFF）：无上游激活信号时，LATS1/2处于非活化状态，YAP/TAZ不被磷酸化，自由进入细胞核与TEAD转录因子结合，启动CTGF、CYR61、Axl等下游靶基因的转录，实现促进细胞增殖、抑制凋亡、维持细胞干性的效应[2]。三、Hippo通路驱动的生理功能与关联疾病 Hippo通路通过调控细胞增殖、分化与存活，在胚胎发育、组织再生及器官稳态中发挥核心作用（见下图）[3]。其失调则广泛参与肿瘤、心血管疾病、肺纤维化、肾病、神经退行性疾病及免疫紊乱等多种病理过程（见下图）[3]。 1. 心血管系统生理功能：YAP在胚胎期促进心肌细胞增殖并调控心脏大小，但成年后Hippo活性抑制再生能力。关联疾病：肥厚型心肌病中YAP激活；扩张型心肌病和心力衰竭中Hippo过度激活；心梗后成纤维细胞中YAP缺失可减轻纤维化并改善心功能。 2. 呼吸系统生理功能：YAP对肺分支形态发生及气道上皮祖细胞增殖分化至关重要。关联疾病：Hippo失活促进肺动脉平滑肌细胞增殖进而驱动肺动脉高压；YAP激活可加重肺纤维化，但在细菌性肺炎中YAP/TAZ激活起保护作用。 3. 消化系统（肝脏）生理功能：肝部分切除后YAP核累积驱动肝再生；MST1/2抑制可增强肝修复。关联疾病：酒精性肝炎和非酒精性脂肪性肝炎中YAP/TAZ升高、Hippo受抑；YAP在肝星状细胞中活化促进肝纤维化，但在缺血-再灌注损伤中起保护作用（上下文依赖性）。 4. 泌尿系统（肾脏）生理功能：YAP参与肾发生，NF2和LATS调控输尿管分支形态发生。关联疾病：Hippo失活致糖尿病肾病中系膜细胞异常增殖；PKD1/2缺陷激活YAP/TAZ驱动多囊肾病囊肿形成；多种肾损伤模型中YAP/TAZ升高促进肾纤维化。 5. 中枢神经系统生理功能：调控神经嵴细胞迁移分化及施万细胞发育、髓鞘形成。关联疾病：阿尔茨海默病、ALS和亨廷顿病中Hippo异常激活，促进神经元死亡；MST1缺失可改善ALS小鼠运动神经元存活。 6. 免疫系统生理功能：YAP负调控I型干扰素应答；MST1/2调控T/B细胞稳态和数量；TAZ影响Th17/Treg平衡。关联疾病：Mst1-Mst2双敲导致自身免疫病；TAZ敲除抵抗自身免疫性脑脊髓炎；临床MST1缺陷患者表现为自身免疫症状。 7. 癌症肿瘤发生与进展：Hippo失活促增殖、抗凋亡，YAP/TAZ驱动代谢重编程和肿瘤干细胞特性；但结直肠癌、ER+乳腺癌等部分肿瘤中YAP反而抑癌（组织特异性）。转移：YAP/TAZ通过诱导EMT促进迁移，并通过抑制失巢凋亡助长转移。耐药：YAP/TAZ过表达或核转位导致化疗耐药（顺铂、5-FU、紫杉醇等）；YAP激活还介导BRAF/MEK/EGFR靶向药及免疫治疗耐药。四、主流药物开发技术路线 Hippo通路与多种疾病密切相关，是极具潜力的治疗靶点，但目前尚无特异性药物获批上市。现有研究主要集中于三大策略： 1.调控Hippo核心激酶（MST/LATS）活性 2.下调YAP/TAZ表达水平 3.破坏YAP/TAZ与TEAD的相互作用其中，抑制核心激酶可促进组织再生，但可能因YAP/TAZ异常激活而带来致癌风险；而阻断YAP-TEAD转录复合物是目前最具前景的方向，相关药物已进入临床试验阶段[3]。格宁生物相关实验我们使用了将携带TEAD特异性响应元件的启动子与萤火虫荧光素酶基因稳定整合至基因组的MCF7人乳腺癌细胞，使荧光素酶的表达完全受TEAD转录因子的调控，通过荧光素酶的发光强度直接量化通路下游TEAD转录因子的激活水平，实现对Hippo通路状态的精准、实时检测。参考文献 Misra JR, Irvine KD. The Hippo Signaling Network and Its Biological Functions. Annu Rev Genet. 2018 Nov 23;52:65-87. doi: 10.1146/annurev-genet-120417-031621. Epub 2018 Sep 5. Feltri ML, Weaver MR, Belin S, Poitelon Y. The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases. J Peripher Nerv Syst. 2021 Mar;26(1):4-16. doi: 10.1111/jns.12431. Epub 2021 Jan 23. Fu M, Hu Y, Lan T, Guan KL, Luo T, Luo M. The Hippo signalling pathway and its implications in human health and diseases. Signal Transduct Target Ther. 2022 Nov 8;7(1):376. doi: 10.1038/s41392-022-01191-9. Erratum in: Signal Transduct Target Ther. 2024 Jan 4;9(1):5. doi: 10.1038/s41392-023-01682-3.

2026-08-25

·院士+

成果推介154｜用于胰腺癌治疗的雷公藤甲素前药TD-1704

克服递药屏障高端制剂全国重点实验室实验室立足国家生物医药战略需求，聚焦口服、静脉和局部给药三大核心用药途径，系统开展突破生理病理学屏障的关键共性科技问题研究。实验室通过多学科交叉融合创新，着力构建系统的克服递药屏障理论体系，注重前沿技术与产业化应用衔接，持续推动高端制剂的基础研究向临床转化。依托四大特色技术平台——克服口服吸收屏障平台、脑部疾病靶向递药平台、病灶靶向仿生纳米制剂平台及其产业化中试平台，实验室近三年成果产出丰硕：发表SCI通讯作者论文400余篇，以第一发明人获授权发明专利58项，取得60个生产批件和1个临床批件(1.1类新药)，制定51项国家化药新药质量标准。其中，原创性靶向抗脑胶质瘤的PDC类前体药物技术，为突破血脑屏障、血脑肿瘤屏障实现化疗药物精准递送提供了全新解决方案，目前该PDC药物(1.1类新药)已进入开发阶段。实验室项目：用于胰腺癌治疗的雷公藤甲素前药 TD-1704 项目/技术简介胰腺癌是一种常见的恶性消化道肿瘤，患者5年生存率低于9%。胰腺癌的临床治疗主要采用手术切除、药物治疗和放射疗法相结合的综合方案，其中药物治疗对胰腺癌而言至关重要。目前胰腺癌临床药物治疗方案包括吉西他滨、AG方案（吉西他滨+白蛋白结合型紫杉醇）和FOLFIRINOX方案（奥沙利铂+伊立替康+亚叶酸钙+ 5-氟尿嘧啶），患者中位生存期均低于12个月。鉴于临床药物对胰腺癌患者生存期没有显著提高，我们启动了雷公藤甲素前药TD-1704的研发项目，旨在为胰腺癌患者提供安全有效的治疗方案。雷公藤甲素是从卫矛科植物雷公藤中提取的一种环氧二萜内酯化合物，通过多靶点作用机制抑制胰腺癌的生长，然而毒副作用大和水溶性差降低了其成药性。TD-1704是一种雷公藤甲素胆碱前药，胆碱基团的引入不仅显著提高了TD-1704的水溶性，同时静脉给药TD-1704可被血浆中丁酰胆碱酯酶水解释放原药雷公藤甲素发挥多靶点抗胰腺癌作用。目前，TD-1704药物已顺利完成概念验证。申请人团队前期已经完成了TD-1704的制备工艺、药物动力学研究、动物模型药效学评价和组织分布学研究。研究结果证实：TD-1704能够显著改善雷公藤甲素的溶解性能；静脉注射TD-1704转化为雷公藤甲素，对于胰腺癌原位瘤和皮下瘤两种动物模型展现出具有良好的抗肿瘤活性，且TD-1704拓展了肿瘤治疗窗。相关成果已申请中国发明专利（中国专利申请号：202110653742.4）。从已获得的实验数据判断，TD-1704的有效性和安全性得到证实，有望实现从概念验证阶段向临床应用阶段过渡。市场需求：2024年全球胰腺癌化疗药物市场规模约为28亿美元，占胰腺癌药物整体市场的62%。2025 年中国胰腺癌化疗药物市场规模约95亿人民币，占国内胰腺癌药物市场的63%。以吉西他滨和氟尿嘧啶类药物为核心品种，国产仿制药占据80%以上市场份额。预测2025~2030年市场规模预计以5.8% 的CAGR小幅增长，达125亿人民币。核心优势 ① 安全性：雷公藤甲素前药TD-1704的治疗指数是雷公藤甲素的2.5倍，拓展了药物治疗窗，可获得良好的安全性； ② 有效性：相较于吉西他滨、紫杉醇和氟尿嘧啶等单靶点胰腺癌临床化疗药物，雷公藤甲素前药TD-1704的多靶点抗肿瘤机制提高了胰腺癌治疗的有效性； ③ 工业化生产：TD-1704合成工艺成熟，可实现大规模工业化生产。主要应用场景适应症：胰腺癌、晚期胃癌等恶性肿瘤给药方式和应用场景：静脉给药，医院成果成熟度原理验证资源需求技术合作技术转让经验丰富的新药研发团队、新药临床研究资金、以及新药上市后的市场推广对合作方式的建议/要求项目转让，里程碑付款，上市后销售额提成如果您对以上科技成果有意向或有意愿与该实验室探讨其他合作，请联系：未来生命健康专业委员会工作人员朴龙虎 13802410122 “百家全重进湾区行动”广东院士联合会的重点工作之一。院士联合会通过设立全国重点实验室大湾区技术转移转化中心、举办全国重点实验室技术成果大湾区对接大会等一系列工作，持续推动全国重点实验室与重点产业、重点企业深度对接，推动更多的科技成果落地转化。院士联合会已面向全国重点实验室征集梳理了一批具有市场潜力及产业化资源需求的科技成果，现分期进行成果推介，并长期开展合作意向征集。欢迎各企事业单位与我们联系，我们将及时组织成果供需双方进行合作对接。热文荐读 ◆ 可持续能源与先进材料产业科技创新交流对接会在穗举行，搭建产学研金对接平台，力促产业科技互促双强 ◆ 广东院士联合会召开会议传达学习习近平总书记在国家科学技术奖励大会、两院院士大会、中国科协第十一次全国代表大会上的重要讲话精神 ◆ 百家全重进湾区行动 | 生物医药与健康产业科技创新对接交流会在南沙召开，产学研精准对接达成多项合作意向 ◆ 广东院士联合会专业委员会｜名单

抗体药物偶联物多肽偶联药物

100 项与氟尿嘧啶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00584	氟尿嘧啶	L01BC02	DB00544

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
胰腺腺癌	美国	Avyxa Pharma LLC	2026-02-20
食管癌	日本	Kyowa Kirin Co., Ltd.	2021-11-25
肠肿瘤	日本	Kyowa Kirin Co., Ltd.	2018-09-21
胆道癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
膀胱癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
结肠癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
胆囊肿瘤	巴西	Libbs Farmacêutica Ltda.	2007-01-22
肝细胞癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
直肠癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
头颈部肿瘤	日本	Kyowa Kirin Co., Ltd.	2005-02-14
鲍恩病	澳大利亚	iNova Pharmaceuticals (Australia) Pty Ltd.	1991-08-23
肿瘤	中国	远大医药（中国）有限公司	1981-01-01
皮肤肿瘤	日本	Kyowa Kirin Co., Ltd.	1972-08-26
光化性角化病	美国	Extrovis AG	1970-07-29
晚期胃癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24
子宫内膜癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24
肝癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24
肺癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24
卵巢癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24
复发性胃癌	日本	Kyowa Kirin Co., Ltd.	1967-07-24

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
RAS/BRAF基因野生型结直肠癌	临床3期	意大利	National Cancer Institute	2024-06-12
皮肤鳞状细胞癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
下咽癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
转移性头颈部鳞状细胞癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
下咽部鳞状细胞癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
喉鳞状细胞癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
口腔鳞状细胞癌	临床3期	美国	ECOG-ACRIN Medical Research Foundation, Inc.	2023-06-08
晚期胃食管交界处腺癌	临床3期	美国	Alliance for Clinical Trials in Oncology	2023-01-31
转移性胃食管腺癌	临床3期	美国	Alliance for Clinical Trials in Oncology	2023-01-31
转移性胃食管结合部腺癌	临床3期	美国	Alliance for Clinical Trials in Oncology	2023-01-31

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05413811 (ACT 2, CTgov)	N/A	子宫颈发育不良 \| 乳头状瘤病毒感染 \| HIV感染 ... 更多	180	5 Fluorouracil (5 FU) Cream (5 Fluorouracil (5FU) Cream)	壓蓋遞製願壓鹽夢餘廠 = 築鏇艱觸鹽蓋醖夢淵顧衊獵範襯網顧範壓鑰鑰 (蓋艱獵醖觸鬱醖願窪齋, 蓋遞蓋觸構網遞製衊鹹 ~ 淵夢膚膚範積糧艱願衊) 更多	-	2026-08-21
				Placebo (Placebo Cream)	壓蓋遞製願壓鹽夢餘廠 = 餘網簾襯鏇簾獵鹽糧獵衊獵範襯網顧範壓鑰鑰 (蓋艱獵醖觸鬱醖願窪齋, 繭膚選築齋願鑰淵遞襯 ~ 齋蓋艱繭製網鹹壓網夢) 更多
ESMO_GI2026 \| ESMO_GCC2026	N/A	胃肠道肿瘤	47	5-FU-based chemotherapy	餘壓齋積觸鏇觸鹹積獵(夢網觸顧齋網願夢廠遞) = 鏇艱願顧夢衊糧範製獵壓網積壓餘繭繭獵積淵 (夢觸鏇製夢顧鏇窪願蓋 ) 更多	积极	2026-07-02
NCT01871571 (CTgov)	临床2期	直肠腺癌	17	laboratory biomarker analysis+leucovorin calcium+bevacizumab+oxaliplatin+fluorouracil	艱廠構糧壓鏇鬱顧壓觸 = 鬱淵鏇膚淵廠鏇觸築鏇網廠鏇鹹壓鑰蓋憲淵齋 (網鹹醖壓築膚繭糧蓋廠, 鏇鏇構觸鹹窪築鬱憲鑰 ~ 鬱顧積範艱積鹽鬱糧製) 更多	-	2026-07-01
ASCO_Breakthrough2026	N/A	食管癌一线	61	modified docetaxel, cisplatin, and fluorouracil (mDCF)	餘醖鏇憲簾觸製夢範鏇(觸繭繭齋願壓構願築願) = 蓋廠鹹觸簾積顧簾願壓艱廠憲壓鬱鹹築簾襯鑰 (築蓋製醖壓顧齋範餘膚 ) 更多	积极	2026-06-25
NCT03698461 (Pubmed \| Genome Med)	临床2期	结肠癌肝转移新辅助	60	ABFOLFOX treatment	獵鏇餘願鏇築繭願簾觸(鹹範艱醖夢鏇窪淵鹹觸) = 衊願鬱餘窪廠築醖窪憲網衊鑰選積糧艱醖鹹襯 (遞簾構醖範鑰醖繭襯鹽 )	积极	2026-05-30
NCT04005339 (NAPOLI-2, ASCO2026)	临床2期	胆道癌二线	48	Nanoliposomal irinotecan + leucovorin + fluorouracil	繭願積蓋餘蓋齋壓襯壓(製築築壓構繭鏇衊選糧) = 淵範膚製餘醖憲鏇淵鹽簾網襯鹽廠鏇壓艱鑰餘 (繭繭窪蓋糧鹹鹽鏇構繭 ) 更多	积极	2026-05-29
ASCO2026	N/A	鼻咽癌	121	TPF chrono-chemotherapy	窪壓膚糧糧鏇窪襯廠蓋(顧鑰鏇蓋齋蓋膚觸襯齋) = The incidence of dysphagia in the chrono-chemotherapy group matched for timing was significantly lower than that in the conventional chemotherapy group, with a statistically significant difference. (P<0.05) 淵積願構簾繭鏇鑰醖積 (壓淵鬱願衊艱鬱鹹廠憲 ) 更多	积极	2026-05-29
				TPF conventional chemotherapy
NCT00082706 (ASCO2026)	临床2期	脐尿管腺癌一线	46	Gemcitabine, 5-fluorouracil/leucovorin, and cisplatin (GemFLP)	構選壓憲積顧簾顧獵構(窪觸蓋憲鑰獵遞鬱衊膚) = 壓構選壓鬱獵範觸糧襯範壓窪鑰壓鑰蓋襯蓋憲 (網膚鏇鑰構艱鏇餘顧醖, 15.9 ~ 35.3) 更多	积极	2026-05-29
				Gemcitabine, 5-fluorouracil/leucovorin, and cisplatin (GemFLP) (urachal)	鏇窪積築廠憲鬱願餘衊(獵遞選顧鬱鏇鹹繭齋網) = 網築鬱選願鑰遞齋鹹餘窪壓夢壓遞願餘襯觸艱 (遞醖壓觸選遞鑰衊製鹹 )
ASCO2026	N/A	复发性头颈癌	180	Cisplatin + 5-fluorouracil	襯憲鑰廠遞願鹽壓選夢(鏇遞窪醖艱鏇鑰築餘醖) = adverse events including vomiting, renal insufficiency, fever, bone marrow suppression, hearing loss, and skin rashes were more frequent with CF 餘繭願積鑰選網遞憲窪 (憲蓋簾繭鹹繭鏇餘築窪 ) 更多	积极	2026-05-29
				Gefitinib
NCT06662006 (ASCO2026)	临床2期	转移性胰腺导管腺癌二线	46	NAL-IRI/5-FU/LV + benmelstobart + anlotinib (Cohort A)	築製鑰網網鏇壓憲積艱(鏇鑰艱糧淵憲觸網遞鏇) = 鬱憲觸鹹顧顧糧襯製憲鏇鏇鏇廠醖糧製網遞選 (淵選網衊鏇糧觸簾選鹽, 1.9 ~ 32.9) 更多	积极	2026-05-29
				NAL-IRI/5-FU/LV + benmelstobart + anlotinib (Cohort B)	築製鑰網網鏇壓憲積艱(鏇鑰艱糧淵憲觸網遞鏇) = 齋糧蓋觸網壓蓋窪獵獵鏇鏇鏇廠醖糧製網遞選 (淵選網衊鏇糧觸簾選鹽, 12.0 ~ 64.9) 更多