沙利雷塞(Salirasib) - 药物靶点：RAS_在研适应症：三阴性乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

S-Farnesylthiosalicyclic acid、Salirasib (INN/USAN)、Transfarnesylthiosalicyclic acid

+ [3]

靶点

RAS

作用方式

抑制剂

作用机制

RAS 抑制剂(RAS type GTPase family inhibitors)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症

三阴性乳腺癌

非在研适应症

急性淋巴细胞白血病急性髓性白血病晚期非小细胞肺癌+ [8]

原研机构

Concordia Pharmaceuticals, Inc.

在研机构

南京医科大学

非在研机构

Ono Pharmaceutical Co., Ltd.Concordia Pharmaceuticals, Inc.

Kadmon Pharmaceuticals LLC

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)临床前

特殊审评孤儿药 (美国)

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结构/序列

分子式C22H30O2S

InChIKeyWUILNKCFCLNXOK-CFBAGHHKSA-N

CAS号162520-00-5

关联

3

项与沙利雷塞相关的临床试验

JPRN-jRCT2080221709

/ Unknown status临床1期

A Phase 1 study of ONO-7056 in patients with solid tumor

开始日期2012-02-13

申办/合作机构

Ono Pharmaceutical Co., Ltd.

NCT00531401

/ Completed临床2期

Salirasib for Treatment of Advanced Non-Small Cell Lung Cancer: a Phase II Study

The purpose of this study is to determine whether Salirasib is effective to shrink or prevent the growth of the tumors associated with non-small cell lung cancer in both patients who are newly diagnosed or have recurrent disease.

开始日期2007-09-01

申办/合作机构

Concordia Pharmaceuticals, Inc.

NCT00867230

/ Completed临床1期IIT

A Phase I Open-Label Study of S-Trans, Trans-Farnesylthiosalicylic Acid (FTS) Administered on Days 1 to 21 of a 28 Day Cycle in Patients With Advanced Hematologic Malignancies

Primary Objective:
Determining the maximum tolerated dose (MTD) and pharmacokinetics (PK) of FTS (S-Trans, Trans-Farnesylthiosalicylic Acid) after daily oral administration on Days 1 through 21 of a 28-Day cycle to patients with advanced hematologic malignancies that have progressed following effective therapy or for which no effective therapy exists.

开始日期2006-05-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与沙利雷塞相关的临床结果

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100 项与沙利雷塞相关的转化医学

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100 项与沙利雷塞相关的专利（医药）

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421

项与沙利雷塞相关的文献（医药）

2026-04-01·ULTRASONICS SONOCHEMISTRY

Bubble coalescence and dissolution effects on sonochemical activity in pulsed wave ultrasound systems

Article

作者: Nolan, Marc C ; Fernandez, Haleigh A ; Fuller, Fallon R ; Weavers, Linda K ; Cowen, Amanda N

Pulsed wave (PW) ultrasound offers a promising alternative to continuous wave (CW) ultrasound for contaminant degradation, yet the mechanisms governing PW sonochemical effectiveness remains underexplored. This study investigates the relative influence of bubble coalescence and dissolution on sonochemical activity in PW systems using calorimetry, terephthalate (TA) dosimetry, and the capillary method. Experiments were conducted at 337 kHz with 10 and 100 ms on-times with varying off-times and surfactant concentrations using fluorotelomer sulfonates (FtS) of differing chain lengths. Calorimetry and hydroxyterephthalate (HTA) fluorescence consistently showed less sonochemical activity with increasing off-times. However, bubble coalescence, measured by the capillary method, decreased with increasing off-times. These findings, taken together, indicate that bubble dissolution, rather than coalescence, is the dominant factor limiting sonochemical efficiency in PW systems. In the presence of FtS and compared to CW systems, PW did not affect bubble coalescence, suggesting surfactants affect bubble coalescence similarly in CW and PW systems. Finally, calorimetry proved to be a reliable, chemical-free dosimeter for assessing cavitation activity, offering a practical alternative to traditional dosimeters.

2026-03-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

A colon-targeted nanozyme-inulin hydrogel system for reactive oxygen species scavenging and gut microbiota modulation in inflammatory bowel disease therapy

Article

作者: Shi, Qingping ; Xu, Jinling ; Zhang, Dan ; Hu, Jiangning ; Luo, Fengxian ; Chen, Lihang ; Chen, Tao ; Wang, Xinchuang

Inflammatory bowel disease (IBD) represents a chronic inflammatory disorder characterized by excessive reactive oxygen species (ROS) generation, persistent inflammatory response, and gut microbiota dysbiosis. Herein, a novel colon-targeted composite hydrogel (FTS/Gel) consisting of metal-polyphenol nanozymes (FTS) embedded in an inulin-based gel was developed for efficient oral treatment of IBD. This nanozyme (FTS) was synthesized by coordination between Fe³⁺ ions and the anti-inflammatory drugs taxifolin (Tax) and L-Se-methylselenocysteine (SeMC), exhibiting remarkable superoxide dismutase (SOD)-like and catalase (CAT)-like activities. Moreover, FTS nanozymes significantly scavenged intracellular ROS and suppressed inflammation in RAW264.7 cells. Incorporating FTS into an inulin hydrogel notably enhanced colon-targeting efficiency, bio-adhesion, and retention time in vivo. Oral administration of FTS/Gel effectively alleviated colitis, as evidenced by increased colon length, reduced splenomegaly, restored intestinal epithelial barrier integrity, and enhanced mucin secretion. Furthermore, FTS/Gel treatment rebalanced gut microbiota composition by promoting beneficial bacteria and suppressing pernicious bacteria. Collectively, this study presents a promising therapeutic strategy combining antioxidant nanozymes and prebiotic-based hydrogel delivery systems for effectively managing and treating IBD.

2026-02-01·METHODS

Establishment and application of a fully automated serum total free sulfhydryl assay based on 2,2′-DTDP

Article

作者: Zeng, Jie ; Zhao, Haijian ; Zhou, Weiyan ; Wang, Jing ; Dong, Jun ; Wang, Siming ; Zhang, Chuanbao ; Zhang, Tianjiao ; Zheng, Hao ; Shao, Zhiyu ; Chen, Wenxiang ; Zhang, Jiangtao

BACKGROUND:

Serum free thiols (FTs) are sensitive biomarkers of oxidative stress, closely associated with aging and chronic disease risk. Existing DTNB-based detection methods suffer from product instability, affecting analytical reliability. A more stable and high-throughput method is needed.

METHODS:

We developed an automated FT assay using 2,2'-dithiodipyridine (2,2'-DTDP) on a clinical chemistry analyzer. Serum samples reacted with 2,2'-DTDP under optimized conditions, and absorbance at 340 nm was used to quantify FT levels. Method performance, stability, and associations with cardiovascular disease (CVD) risk factors were assessed in 341 healthy individuals.

RESULTS:

FTs reacted with 2,2'-DTDP to generate 2-TP, a stable product with maximum absorbance at 340 nm. The method demonstrated excellent linearity (0-1200 μmol/L), low imprecision (1.8 %-3.3 %), and reasonable recovery (≥80 %). Serum FTs were stable for at least one year at -70 °C, 12 h at 2-8 °C, and 2 h at room temperature. In the study population, FT levels were positively correlated with serum albumin, a major thiol carrier, and negatively correlated with age, triglyceride, glucose and creatinine, suggesting links to redox status and CVD risks. These associations support the potential of FTs as indicators of systemic oxidative balance and aging-related health decline.

CONCLUSION:

This simple and robust 2,2'-DTDP-based method enables accurate, high-throughput measurement of serum FTs. It is well suited for exploring thiol antioxidant function and evaluating age-related and cardiovascular risk in clinical and research settings.

1

项与沙利雷塞相关的新闻（医药）

2025-09-30

·今日头条

“最毒乳腺癌”治疗有新招！南京医科大学与苏州大学合作使肿瘤体积大减

【导读】三阴性乳腺癌 (TNBC) 缺乏激素受体和 HER2 表达，在乳腺癌治疗中带来了巨大的治疗挑战。免疫治疗的疗效经常受到肿瘤微环境 (TME) 免疫抑制特性的影响。因此，发现有效的靶点以阻止 TNBC 进展并增强免疫治疗的有效性是至关重要的。 9月29日，南京医科大学/苏州大学研究人员合作共同在期刊《Clinical And Translational Medicine》上发表了研究论文，题为“Targeting c-Myc enhances immunotherapy efficacy in combination with Ras inhibitor in triple-negative breast cancer”，本研究中，研究人员在三阴性乳腺癌（TNBC）中观察到 c-Myc 表达升高，从细胞周期药物库中鉴定出的 Ras 抑制剂沙利雷塞被确认为在 c-Myc 过表达的 TNBC 中具有强大协同作用的药物。沙利雷塞与 c-Myc 敲低联合应用显著抑制了体外肿瘤细胞的侵袭性并诱导其凋亡。在体内，这种联合疗法显著提高了 PD-L1 阻断的疗效，导致小鼠 TNBC 模型中肿瘤体积缩小、肺转移抑制以及免疫微环境重塑。 https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70484 研究背景 01 三阴性乳腺癌（TNBC）是指缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）表达的乳腺癌亚型，是所有乳腺癌中最具侵袭性的类型，也被称为“最毒乳腺癌”。TNBC 占所有乳腺癌病例的 15% 至 20%，TNBC 的异质性以及有效治疗靶点的缺乏进一步增加了治疗的复杂性。因此，化疗仍是 TNBC 治疗的主要手段。在最近的几项临床试验中，免疫疗法被认为是一种可行的治疗方案；然而，结果喜忧参半，往往不尽人意。试验表明了免疫检查点抑制剂（ICIs）在治疗方面的巨大潜力，但也表明其在三阴性乳腺癌（TNBC）中的疗效存在差异且有限，这强调了进一步阐明 TNBC 的肿瘤微环境（TME）并确定有效靶点以增强 ICIs 协同作用的必要性。上述见解证明了探索新的治疗策略以提高 ICIs 反应性的合理性。靶向 c-Myc 联合 Salirasib 能协同抑制三阴性乳腺癌细胞的侵袭和迁移 02 三阴性乳腺癌（TNBC）具有侵袭性强和易转移的特点，这凸显了抑制肿瘤细胞侵袭和远处转移的治疗意义至关重要。为了阐明这一点，研究人员采用迁移实验发现，联合治疗组显著抑制了细胞侵袭，而单药治疗组则不然。此外，通过伤口愈合实验观察到，协同治疗组中三阴性乳腺癌细胞的迁移能力显著降低。研究人员进一步分析了迁移蛋白的表达情况。靶向抑制 c-Myc 和沙利雷塞单药治疗均增强了 E-钙粘蛋白的表达，同时抑制了 MMP-9、MMP-2 和波形蛋白的表达。尤其是，联合治疗对这些蛋白的表达水平产生了更显著的影响。这些发现表明，靶向 c-Myc 和 Salirasib 的协同作用可能有效抑制三阴性乳腺癌细胞的侵袭和迁移。此外，研究结果表明，用沙利雷塞处理 shc-Myc 三阴性乳腺癌细胞可显著降低上皮间质转化（EMT）。这种减少程度明显比任何单一疗法都更为显著，进一步证实了这两种疗法之间的协同作用。总之，这些发现表明，联合抑制 c-Myc 和靶向 Ras 通路不仅能抑制三阴性乳腺癌细胞的侵袭和迁移，而且为限制三阴性乳腺癌的转移提供了一种很有前景的策略。沙利雷塞与靶向 c-Myc 联合使用协同抑制三阴性乳腺癌细胞迁移和侵袭结论 03 总之，本研究通过药物库筛选方法发现，在 c-Myc 过表达的三阴性乳腺癌细胞中，抑制 c-Myc 与 Salirasib 联合使用具有协同抗肿瘤作用。这种组合显著增强了抗肿瘤活性和免疫治疗效果。在原发性和转移性三阴性乳腺癌模型中的体内验证进一步证实了其治疗潜力。这些发现为增强 c-Myc 阳性三阴性乳腺癌免疫治疗效果的潜在联合方法提供了证据。参考资料： https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70484 2025年12月09-12日中国 • 上海

免疫疗法临床结果临床终止AACR会议

100 项与沙利雷塞相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08995	-	-	DB12681

研发状态

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
晚期非小细胞肺癌	临床2期	美国	Concordia Pharmaceuticals, Inc.	2007-09-01
非小细胞肺癌	临床2期	-	Ono Pharmaceutical Co., Ltd.	-
胰腺癌	临床2期	-	Ono Pharmaceutical Co., Ltd.	-
急性淋巴细胞白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
急性髓性白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
慢性淋巴细胞白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
慢性粒细胞性白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
慢性粒单核细胞白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
骨髓增生异常综合征	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01
难治性白血病	临床1期	美国	Concordia Pharmaceuticals, Inc.	2006-05-01

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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


ASCO2009	临床2期	-	33	Salirasib	艱襯艱夢觸繭廠觸鑰艱(艱製鏇網憲範簾鹹餘憲) = 鏇衊夢鑰顧衊窪糧壓鏇蓋醖願選範選構構齋鏇 (壓壓鬱鬱遞艱選廠獵艱 ) 更多	-	2009-05-20