An Open Label, Single-Arm, Phase I Exploratory Trial to Assess the Safety and Preliminary Efficacy of mFOLFIRINOX with Hydroxychloroquine and Chlorphenesin carbamate in Patient with in Inoperable Locally Advanced or Metastatic Pancreatic Cancer

开始日期2021-12-21

申办/合作机构

Asan Medical Center

100 项与氯苯甘醚相关的临床结果

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100 项与氯苯甘醚相关的转化医学

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100 项与氯苯甘醚相关的专利（医药）

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173

项与氯苯甘醚相关的文献（医药）

2025-02-01·RAPID COMMUNICATIONS IN MASS SPECTROMETRY

Detection and Identification of New Chlorphenesin Carbamate Metabolites in Human Urine and Metabolomic Characterization Using Liquid Chromatography‐Q Exactive‐HF‐Orbitrap‐Mass Spectrometry

Article

作者: Liu, Bing ; Xu, Siyan ; Xu, Wennuo ; Niu, Bing ; Zhuo, Yue ; Deng, Xiaojun ; Li, Zhongquan

ABSTRACT:

Chlorphenesin carbamate is a skeletal muscle relaxant, and one of its metabolites is 4‐chlorophenoxyacetic acid (4‐CPA), which is included on the Prohibited List of the World Anti‐Doping Agency (WADA). The non‐prohibited substance, chlorphenesin carbamate, as a potential source of 4‐CPA, needs to be identified more strongly in doping control protocols. In this paper, the metabolism of chlorphenesin carbamate in human urine was studied. Ten volunteers were recruited to take chlorphenesin carbamate tablets orally, and urine samples were collected before and after being tested. The urine samples were detected by liquid chromatography‐Q Exactive HF orbitrap mass spectrometry (LC‐Q Exactive HF‐MS) in full MS and full MS‐ddMS2 scanning modes. Based on accurate molecular formulae determination and fragmentation pattern analysis by mass spectrometry, a total of 29 chlorphenesin carbamate metabolites were found, comprising 18 newly identified metabolites and 11 previously reported metabolites. There were five potential metabolic processes listed: hydroxylation, amide hydrolysis, C‐oxidation, O‐glucuronidation, sulfation, and their combinations. Chlorphenesin carbamate and the 29 metabolites were compared for their detection windows, and the findings indicated that the two recently reported metabolites, M9 and M10, had longer detection windows than the metabolites documented by the WADA. These metabolites are anticipated to be long‐lasting biomarkers for the detection of chlorphenesin carbamate intake. By analyzing the results of metabolomic profiling, it was found that the metabolites with significant changes were mainly related to histidine metabolism and β‐alanine metabolism pathways. This paper provides a comprehensive report on the metabolic profile of urinary chlorphenesin carbamate and reveals a point of view the changes in the metabolic in the human body, which is conducive to supporting the detection of chlorphenesin carbamate and meclofenoxate for doping control, as well as a better understanding of the mechanism of action of chlorphenesin carbamate as a drug.

2024-11-01·Biological trace element research

Boric Acid and Borax Protect Human Lymphocytes from Oxidative Stress and Genotoxicity Induced by 3-Monochloropropane-1,2-diol

Article

作者: Tozlu, Ozlem Ozdemir ; Mardinoglu, Adil ; Saracoglu, Muhammed Melik ; Turkez, Hasan ; Baba, Cem ; Tatar, Abdulgani ; Arslan, Mehmet Enes ; Yıldız, Edanur

Abstract:

3-chloro-1,2-propanediol (3-MCPD) is a member of the group of pollutants known as chloropropanols and is considered a genotoxic carcinogen. Due to the occurrence of 3-MCPD, which cannot be avoided in multiplexed food processes, it is necessary to explore novel agents to reduce or prevent the toxicity of 3-MCPD. Many recent studies on boron compounds reveal their superior biological roles such as antioxidant, anticancer, and antigenotoxic properties. In the current investigation, we have evaluated in vitro cytotoxic, oxidative, and genotoxic damage potential of 3-MCPD on human whole blood cultures and the alleviating effect of boric acid (BA) and borax (BX) for 72 h. In our in vitro experiments, we have treated blood cells with BA and BX (2.5, 5, and 10 mg/L) and 3-MCPD (at IC50 of 11.12 mg/l) for 72 h to determine the cytotoxic damage potential by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) release assays. Oxidative damage was assessed using total antioxidant capacity (TAC) and malondialdehyde (MDA) levels. Genotoxicity evaluations were performed using chromosome aberrations (CAs) and 8-hydroxy deoxyguanosine (8-OHdG) assays. The result of our experiments showed that the 3-MCPD compound induced cytotoxicity, oxidative stress, and genotoxicity in a clear concentration-dependent manner. BA and BX reduced cytotoxicity, oxidative stress, and genotoxicity induced by 3-MCPD. In conclusion, BA and BX are safe and non-genotoxic under the in vitro conditions and can alleviate cytotoxic, oxidative, and genetic damage induced by 3-MCPD in the human blood cells. Our findings suggest that dietary boron supplements may offer a novel strategy for mitigating hematotoxicity induced by xenobiotics, including 3-MCPD.

2024-09-01·REPRODUCTIVE TOXICOLOGY

3-chloro-1,2-propanediol induces oxidative stress and promotes testicular damage and infertility in rats through CYP2C9

Article

作者: Li, Xue ; Fu, Kai ; Xue, Boxin ; Zhang, Hong ; Gao, Chuchu

3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.

100 项与氯苯甘醚相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00770	氯苯甘醚	D01AE07	DB14656

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
颈臂综合征	日本	Taisho Pharmaceutical Co., Ltd.	1986-06-01
背痛	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
腰痛	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
骨质疏松症	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
脊椎滑脱症	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13
退化性脊椎炎	日本	Taisho Pharmaceutical Co., Ltd.	1979-03-13