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PhaseⅠstudy of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up 被引量:2
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作者 Zhuang Kang Shan Li +6 位作者 Xun Kang Jing Deng Huarong Yang Feng Chen Jiandong Jiang Jie Zhang Wenbin Li 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第6期465-476,共12页
Objective:This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid(CGA)in patients with recurrent high-grade glioma after standard of care treatments,through a first-in-human... Objective:This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid(CGA)in patients with recurrent high-grade glioma after standard of care treatments,through a first-in-human,open-label,dose-escalation phase I trial.Methods:A total of 26 eligible patients were enrolled,received intramuscular CGA injections at 5 dose levels,and were followed up for 5 years.CGA was well tolerated,and the maximum tolerated dose was 5.5 mg/kg.Results:The most common treatment-related adverse events occurred at the sites of injection.No grade 3 or 4 adverse events(e.g.,drug allergy)were reported for these patients except for induration at the injection sites.A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma,with a t_(1/2)of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30,and no detectable CGA was observed on days 9,11,13,23,25,27,and 29 before CGA administration.After the first treatment cycle,52.2%of patients(12 of 23)achieved stable disease.Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients.Of the 18 patients with grade 3 glioma,the median overall survival was 9.5 months.Two patients remained alive at the cutoff day.Conclusions:This phase I study demonstrated that CGA has a favorable safety profile(with no severe toxicity),and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies,thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma. 展开更多
关键词 INJECTION GLIOMA TREATMENT
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Target fishing and mechanistic insights of the natural anticancer drug candidate chlorogenic acid
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作者 Qinghua Wang Tingting Du +6 位作者 Zhihui Zhang Qingyang Zhang Jie Zhang Wenbin Li Jian-Dong Jiang Xiaoguang Chen Hai-Yu Hu 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第10期4431-4442,共12页
Chlorogenic acid(CGA)is a natural product that effectively inhibits tumor growth,demonstrated in many preclinical models,and phase II clinical trials for patients with glioma.However,its direct proteomic targets and a... Chlorogenic acid(CGA)is a natural product that effectively inhibits tumor growth,demonstrated in many preclinical models,and phase II clinical trials for patients with glioma.However,its direct proteomic targets and anticancer molecular mechanisms remain unknown.Herein,we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)was one of the main target proteins of CGA by using affinity-based protein profiling(AfBPP)chemical proteomic approach.We performed in-depth studies on ACAT1/CGA interactions via multiple assays including SPR,ITC,and cryo-EM.Importantly,we demonstrated that CGA impaired cancer cell proliferation by inhibiting the phosphorylation of tetrameric ACAT1 on Y407 residue through a novel mode of action in vitro and in vivo.Our study highlights the use of AfBPP platforms in uncovering unique druggable modalities accessed by natural products.And identifying the molecular target of CGA sheds light on the future clinical application of CGA for cancer therapy. 展开更多
关键词 AfBPP Natural product Chlorogenic acid PROBE ACAT1
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