This is a Phase II, single center study measuring the pharmacokinetic parameters of NDGA administration and assessing the proportion of patients who experience a 50% decline in PSA.

开始日期2008-05-01

申办/合作机构

The University of California, San Francisco

[+1]

NCT00313534

/ Terminated临床1期IIT

A Phase I Study of NDGA in Patients With Non-Metastatic Biochemically Relapsed Prostate Cancer

RATIONALE: Nordihydroguaiaretic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of nordihydroguaiaretic acid in treating patients with nonmetastatic relapsed prostate cancer.

开始日期2005-06-01

申办/合作机构

The University of California, San Francisco

[+1]

100 项与马索罗酚相关的临床结果

登录后查看更多信息

100 项与马索罗酚相关的转化医学

登录后查看更多信息

100 项与马索罗酚相关的专利（医药）

登录后查看更多信息

2,201

项与马索罗酚相关的文献（医药）

2025-12-31·Gut Microbes

Gut microbial Nordihydroguaiaretic acid suppresses macrophage pyroptosis to regulate epithelial homeostasis and inflammation

Article

作者: Lin, Zelong ; Wang, Zezheng ; Zhang, Beiping ; Zhang, Haiyan ; Wang, Jun ; Tan, Huishi ; Weng, Senhui ; Li, Jierui ; Liu, Hongbin ; Huang, Linwen ; Tang, Jing ; Xu, Jiahui ; Ye, Ziwen ; Huang, Chongyang ; Luo, Huishan ; Zhong, Cailing ; Shi, Yanqiang ; Zhai, Luyue

BACKGROUND:

Aging is associated with increased severity of inflammatory bowel disease (IBD). Gut senescence and altered environmental factors contribute to changes in the intestinal metabolome, particularly in frail older individuals. However, the role of age-associated dysbiosis, characterized by a decline in beneficial gut microbiota and their metabolites, in exacerbating IBD remains unclear.

METHODS:

To investigate the impact of aging-associated dysbiosis on colitis development, we employed fecal microbiota transplantation (FMT) in wild-type and IL-10-deficient mice. Aged mice were treated with gut microbiota from either young or aged mice and then subjected to dextran sulfate sodium (DSS) to induce experimental colitis. 16S rDNA sequencing and metabolomics were used to analyze microbial and metabolite profiles. Single-cell RNA sequencing (scRNA-seq) was performed to characterize lamina propria CD45⁺ immune cell composition.

RESULTS:

Aged mice receiving microbiota from young mice exhibited less severe colitis than those receiving microbiota from aged mice, as evidenced by reduced disease activity, weight loss, and colonic shortening. Besides, aged mice displayed a significant decrease in the Lactobacillus population, accompanied by a reduction in Nordihydroguaiaretic acid (NDGA) levels. Decreased fecal NDGA levels were also observed in both IBD patients and elderly individuals. Administration of NDGA alleviated experimental colitis by downregulating the GSDMD/NR4A1/NLRP3 axis-mediated macrophage pyroptosis. Deletion of GSDMD in macrophages significantly diminished the protective effect of NDGA on colitis.

CONCLUSIONS:

Our findings demonstrate that aging is associated with dysbiosis and reduced NDGA production, which increases susceptibility to intestinal inflammation. Gut microbial NDGA exhibits potential anti-inflammatory activity in colitis, suggesting a promising therapeutic target for aged-related IBD.

2025-08-01·BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of novel inhibitors for malate synthase of Mycobacterium Tuberculosis from natural products

Article

作者: Jiang, Qihua ; Wu, Yuchen ; Yang, Xiaolan ; Liao, Lingbing ; Lan, Haoyang ; Niu, Yanhong ; Qi, Guorong ; Hu, Qianfang ; Wu, Zhili

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat, particularly due to dormant Mtb, which necessitates prolonged drug treatment. Mycobacterium tuberculosis malate synthase (MtbMS) is a key rate-limiting enzyme in the glyoxylate shunt, essential for the survival of dormant Mtb but absent in the host. Using target-based virtual screening and biochemical approaches, we identified novel natural inhibitors of MtbMS. Molecular docking by Schrödinger and subsequent manual selection identified 11 compounds as potential inhibitors. Molecular dynamics (MD) simulations and binding-free energy analysis (MM/GBSA) demonstrated high stability and binding affinity of MtbMS with Nordihydroguaiaretic Acids (NDGA) and Meso-NDGA. NDGA and Meso-NDGA by inhibition experiment exhibited half-maximal inhibitory concentrations (IC₅₀) against MtbMS at 1.10 ± 0.01 μM and 14.29 ± 0.95 μM and by Isothermal Titration Calorimetry (ITC) showed binding constants (K_d) of 5.66 μM and 34.90 μM, respectively. Their minimum inhibitory concentrations (MIC) against Mtb H37Rv were 60.47 μg/mL and 30.24 μg/mL, respectively. In conclusion, natural products NDGA and Meso-NDGA are potent inhibitors of MtbMS and represent promising new scaffolds for combating dormant Mtb.

2025-08-01·JOURNAL OF HEPATOLOGY

Hepatocellular CMPK2 promotes the development of metabolic dysfunction-associated steatohepatitis

Article

作者: Liao, Lei ; Zhu, Sitong ; Liu, Zhenming ; Lu, Junfeng ; Xu, Xiaojun ; Zhong, Yi ; Xiao, Yibei ; Yang, Zhiwei

BACKGROUND & AIMS:

There are limited pharmacological treatment options for metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we aimed to identify novel therapeutic targets.

METHODS:

The Gene Expression Omnibus database and human liver tissues obtained from patients with MASH were used to identify differentially expressed genes in MASH. The functional role of cytidine/uridine monophosphate kinase 2 (CMPK2) was assessed in mice with hepatocyte-specific overexpression, conditional knockout mice, and several murine MASH models. CMPK2 inhibitors were discovered through surface plasmon resonance imaging coupled with indirect enzyme activity detection.

RESULTS:

CMPK2, a critical enzyme involved in mitochondrial DNA synthesis, exhibited significant upregulation in the livers of obese individuals with MASH and mice with diet-induced MASH. Hepatocyte-specific Cmpk2 deletion substantially mitigated liver injury, inflammation, and fibrosis in mice. Inhibition of CMPK2, either through genetic manipulation or pharmacological intervention with nordihydroguaiaretic acid, suppressed Nlrp3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation and subsequent hepatic pyroptosis. Furthermore, nordihydroguaiaretic acid alleviated diet-induced metabolic disorders, inflammation, and fibrosis in vivo.

CONCLUSIONS:

These findings establish CMPK2 as a critical mediator in the progression from metabolic dysfunction-associated steatotic liver to MASH and highlight its potential as a therapeutic target for metabolic diseases.

IMPACT AND IMPLICATIONS:

Cytidine/uridine monophosphate kinase 2 (CMPK2) is upregulated in the metabolic dysfunction-associated steatohepatitis (MASH) stage but not in the early stages of metabolic dysfunction-associated steatotic liver disease. Our study demonstrated that diet-induced MASH phenotypes, including liver injury, inflammation, and fibrosis were alleviated in hepatocyte-specific Cmpk2-knockout mice. These findings suggest that CMPK2 serves as a critical link in the progression of steatotic liver to steatohepatitis, offering novel mechanistic insights into MASH development. Furthermore, this discovery identified CMPK2 as a promising target for the development of therapeutic drugs for MASH.

项与马索罗酚相关的新闻（医药）

2023-09-10

·CPHI制药在线

5-脂氧合酶及其抑制剂研究进展

关注并星标CPHI制药在线脂氧合酶是一类非血红素含铁双加氧酶，存在于动、植物的组织和细胞中，可催化花生四烯（AA）、二十二碳六烯酸和各种多不饱和脂肪酸(polyunsaturated fatty acid，PUFA)的氧化反应。脂氧合酶主要分为1、3、5、8、12、15-脂氧合酶6种亚型。其中5-脂氧合酶(5-lipoxygenase，5-LOX)是脂氧合酶同工酶中最常见的、研究较为深入的非血红素铁蛋白氧化代谢酶，是许多高活性氧化脂质生物合成中的关键酶。5-LOX作用于AA氧化通过两步完成：第一步使5-LOX氧化成5-羟过氧化二十碳四烯酸（5-HPETE）再转化为5-羟基二十碳四烯酸（5-HETE）。第二步催化5-HPETE生成白三烯A4(leukotriene A4，LTA 4 )。LTA 4既可转化为致炎物白三烯B4(leukotriene B4，LTB4)，也可生成白三烯C4(leukotriene C4，LTC4)进而生成白三烯D4(leukotriene D4，LTD4)、白三烯E4(leukotrieneE4，LTE4)等导致过敏反应的反应物质。白三烯物质（LT）是哮喘、慢性阻塞性肺疾病、炎症性肠病、关节炎、动脉粥样硬化、皮炎和癌症等多种慢性炎症性疾病相关的促炎性脂质介质，通过进一步的双加氧作用和对外源化学物的协同氧化作用，在炎症、哮喘、脑缺血、部分恶性肿瘤及阿尔茨海默症等疾病的发生和发展中具有极其重要的作用。5-LOX抑制剂通过阻断LT的产生，抑制AA转变为LT，从而减少炎症的产生。因此，开发有效的5-LOX抑制剂对治疗上述疾病至关重要。根据抑制剂的作用机制可将5-LOX抑制剂分为直接抑制剂和间接抑制剂。直接抑制剂直接抑制剂主要针对5-LOX分子结构特点进行研发，比如干扰5-LOX C-端催化结构域中Fe2+与Fe3+正常的转换，或者是与铁离子络合来抑制5-LOX的活性。直接抑制剂包括氧化还原抑制剂、非氧化还原抑制剂、铁离子配体抑制剂。间接抑制剂主要是围绕FLAP进行设计，在5-LOX途径中需要FLAP的参与，抑制了FLAP 就能阻断 5-LOX 途径。 1、氧化还原抑制剂氧化还原抑制剂一般是亲脂性的小分子芳香族化合物，例如酚类化合物和醌类化合物。1,4-苯醌AA-861是第一批氧化还原型5-LOX抑制剂，经多项研究证实其在体内可产生抗炎作用，并已经通过了预防季节性过敏性鼻炎的临床试验。苯醌衍生物在人类单核细胞、中性粒细胞和整个人类血液中可作为5-LOX的有效活性抑制剂，对两种LT相关炎症标准化动物模型的实验研究表明，新型1,4-苯醌RF-Id能够通过抑制LT的产生，在体内抑制导致抗炎反应的5-LOX。此外，氧化还原抑制剂还包括去甲二氢愈创木酸 (NDGA)、香豆素、黄酮类化合物等几类物质，它们均在体外实验证实具有高效的5-LOX 抑制作用。氧化还原抑制剂能把Fe3+还原为Fe2+，从而干扰了铁离子的正常催化循环，阻止5-LOX 的激活，导致5-LOX途径不能正常进行。此外，黄酮类的某些化合物，例如槲皮素、芦丁由于B环上具有邻位的酚羟基，他们还能与Fe3+络合，从而加大了对 5-LOX 的抑制作用。另外，研究人员用荧光法测定了氧化还原抑制剂的氧化还原电势，并揭示了氧化还原抑制剂的作用机制，当氧化还原抑制剂存在时，它降低了Fe2+与Fe3+之间的转换，抑制了酶催化反应，从而需要更多的脂质过氧化物去氧化Fe2+转变成 Fe3+，因此，在酶催化反应过程中，真正参与催化反应的脂质过氧化物的量是很少的，酶催化反应即被抑制。 2、非氧化还原抑制剂非氧化还原抑制剂属于竞争型抑制剂，它能与底物AA竞争结合到5-LOX 的活性中心，导致5-LOX途径受阻，相对于其他抑制剂具有更高的选择性，但是磷酸化作用和Ca2+会干扰这些抑制剂。ZD2138 和ZM230487属于非氧化还原抑制剂中的两个代表。它们属于甲氧基四氢吡喃衍生物，临床研究表明，ZD2138 能够有效抑制关节炎和哮喘病。实验研究表明，一些天然产物和ZD2138 的杂交体 L-697198，以及通过对L-697198结构进行优化而得到的L-708780和L-739010，表现出良好的生物利用度。但后续动物实验发现，该种抑制剂有多种毒性，限制了它的临床使用。此外，L-739,010、CJ-13,610和PF-419183也是非氧化还原型5-LOX抑制剂，在细胞测定中显示IC50的低纳摩尔范围。L-739,010可以减少LT介导的炎症反应，且其抗痛觉亢进活性与炎症大脑中LT水平降低有关，在急性卡拉胶模型和慢性炎症模型中表现出优异的药效和药代动力学，但难以形成共价蛋白结合代谢物。CJ-13,610在大鼠内侧半月板横切面模型上对骨关节炎疼痛有抑制作用，口服CJ-13,610可逆转该动物模型的两种疼痛模式，包括触觉异位痛和负重差异。通过大鼠气囊模型证明了PF-4191834对LTB4产生的抑制作用，PF-4191834也完成了哮喘的Ⅱ期临床试验，但其用于膝骨关节炎的Ⅱ期临床试验因出现晕厥、急性肝炎和胃溃疡出血等严重不良事件而被终止。 3、铁离子配体抑制剂铁离子配体抑制剂大体包括两种，异羟基肟酸类和羟基脲类，羟肟酸衍生物BWA4C和羟基脲衍生物Zileuton是有效的口服5-LOX抑制剂。BWA4C是溃疡性结肠炎患结肠组织中LTB4合成的有效选择性抑制剂，以BWA4C为代表的乙酰异羟肟酸5-脂氧合酶抑制剂有助于评价LTB4在溃疡性结肠炎中的临床意义，并为该病的治疗提供新的途径。Zileuton使急性和慢性气道功能得到了改善，也减少了β受体激动剂或糖皮质激素的需求，并在美国被批准用于治疗哮喘，但是对于变应性鼻炎、类风湿关节炎和炎症性肠病的治疗潜力较低，并且它有许多缺点，如肝毒性和不良药代动力学特征等。以Zileuton结构为基础设计出了一种新型抑制剂VIA-2291，可以在支气管痉挛动物模型中表现出比Zileuton高5倍的效力，口服半衰期16 h，对哮喘患者的运动性支气管收缩有一定的疗效。VIA-2291已成功完成动脉粥样硬化和心血管疾病的Ⅱ期临床试验，成为临床开发中领先的5-LOX抑制剂之一。RBX-7796是一种具有十二烷基链的尿素衍生物，可抑制大鼠血液中LTB4的体外合成，并对各种炎症和支气管收缩动物模型有活性。间接抑制剂间接抑制剂不直接抑制5-LOX的活性。FLAP是5-LOX 激活蛋白，它能结合底物 AA 并且把它转移给5-LOX。在细胞中，5-LOX 与 FLAP 是共同表达的。当给予足够的底物 AA，如果缺少FLAP，细胞也不能合成白三烯等物质。MK886 是研发出来的第一代间接抑制剂，同时也是第一个用于临床的间接抑制剂。它能与AA竞争FLAP 上的结合位点，导致5-LOX 无法与FLAP 相互结合，5-LOX 途径因此受阻。此外，抑制剂AM803正在进行临床实验，并已经完成了对哮喘病人的二期阶段试验，它的衍生物AM103也成功通过了一期临床实验。不过研发的某些抑制剂也存在问题，如NGDA和MK0591 等也存在两方面的缺陷，一是不能特异性针对5-LOX，对人体正常的代谢也有一定的干扰，从而限制了临床应用；二是稳定性不够，直接影响抑制剂的抑制效力。参考资料 [1]李丹凤,范涛,鹿欣雨.5-脂氧合酶抑制剂的研究进展[J].生命的化学,2023,43(05):666-673. [2]黄凯,蒋世云,陈柳军.5-脂氧合酶及其抑制剂[J].中国生物化学与分子生物学报,2014,30(12):1190-1196. 作者简介：小泥沙，食品科技工作者，食品科学硕士，现就职于国内某大型药物研发公司，从事营养食品的开发与研究。智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床1期核酸药物

100 项与马索罗酚相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D04862	马索罗酚	L01XX10	DB00179

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
光化性角化病	美国	University of Arizona Cancer Center	1992-09-04

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00678015 (CTgov)	临床2期	复发性前列腺癌	12	Nordihydroguaiaretic Acid (NDGA)	鏇範構餘鹽齋窪積醖醖 = 蓋網壓廠觸齋顧築糧壓鏇簾淵積獵壓範網鹹築 (願壓選積築範鹽衊窪蓋, 築淵簾壓糧簾範積築憲 ~ 艱鑰積夢構蓋築壓艱網) 更多	-	2014-04-09
NCT00678015 (Pubmed \| Oncol Rep)	临床2期	去势敏感前列腺癌	12	Nordihydroguaiaretic acid (NDGA) 2000 mg	蓋廠壓築蓋蓋範選鹹蓋(夢膚鑰願鏇選襯淵鏇遞) = 簾網鏇艱範鬱醖鏇餘衊蓋積獵繭鹽製淵膚淵鹽 (齋築夢醖鑰鏇獵築簾簾 ) 更多	-	2012-01-01
ASCO2010	临床2期	-	28	Nordihydroguaiaretic acid 2000mg	淵壓糧艱淵膚醖遞繭糧(獵觸願範齋觸膚獵糧鏇) = All grade 3 events occurred in 1 patient and included nausea/vomiting, cognitive disturbance, syncope due to dehydration, and elevated liver function tests 遞顧顧醖鬱簾齋簾選簾 (齋鑰構顧積壓觸構艱繭 )	-	2010-05-20