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Chinese Journal of Natural Medicines 2019年第2期17卷 155-160页

作者： XIONG Lei CHEN Chang-Fa MIN Tao-Ling HU Hai-Feng State Key Lab of New Drug&Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry China State Institute of Pharmaceutical Industry

Romipeptides A and B(1 and 2),two new romidepsin derivatives,and three known compounds,chromopeptide A(3),romidepsin(4)and valine-leucine dipeptide(5)were isolated from the fermentation broth of Chromobacterium violaceum *** structures were elucidated by interpretation of their UV,HR-ESI-MS and NMR *** absolute configuration of compound 1 and 2 were established by single crystal X-ray diffraction *** 1–5 were evaluated for their anti-proliferative activities against three human cancer cell lines,SW620,HL60,and *** results showed most of these compounds exhibited antitumor activities in vitro,in which compound 2 displayed potent cytotoxicity to SW620,HL60 and A549 cell lines,with IC_(50) of 12.5,6.7 and 5.7 nmol·L^(–1),respectively.

关键词： Chromobacterium violaceum romidepsin derivatives Cytotoxicity

Histone Deacetylase Inhibitors romidepsin and Vorinostat Promote Hepatitis B Virus Replication by Inducing Cell Cycle Arrest

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 160-168页

作者： Yang Yang Yu Yan Zhen Chen Jie Hu Kai Wang Ni Tang Xiaosong Li Zhi Zhou Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina Clinical Molecular Medicine Testing Center The First Affiliated HospitalChongqing Medical UniversityChongqingChina Department of Infectious Diseases The Second Affiliated HospitalChongqing Medical UniversityChongqingChina

Background and Aims:Chronic hepatitis B virus(HBV)infection is a global public health *** reactivation usually occurs in cancer patients after receiving cytotoxic chemotherapy or immunosuppressive ***(FK228)and vorinostat(SAHA)are histone deacetylase inhibitors(HDACi)approved by the Food and Drug Administration as novel antitumor *** aim of this study was to explore the effects and mechanisms of HDACi treatment on HBV ***:To assess these effects,human hepatoma cell lines were cultured and cell viability after FK228 or SAHA treatment was measured by the CCK-8 cell counting kit-8 ***,HBV DNA and RNA were quantified by real-time PCR and Southern ***,analysis by western blotting,enzyme-linked immunosorbent assay(ELISA),immunohistochemistry,and flow cytometry was ***:FK228/SAHA treatment significantly promoted HBV replication and biosynthesis in both HBV-replicating cells and HBV-transgenic mouse *** cytometry assay indicated that FK228/SAHA enhanced HBV replication by inducing cell cycle arrest through modulating the expression of cell cycle regulatory *** addition,simultaneous inhibition of HDAC1/2 by FK228 promoted HBV replication more effectively than the broad spectrum HDAC inhibitor ***:Overall,our results demonstrate that cell cycle blockage plays an important role in FK228/SAHAenhanced HBV replication,thus providing a potential avenue for rational use of HDACi in patients with chronic hepatitis B.

关键词： HBV reactivation Histone deacetylase inhibitor romidepsin Vorinostat Cell cycle

romidepsin:治疗皮肤T细胞淋巴瘤的新药

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中国新药与临床杂志 2011年第1期30卷 1-4页

作者：张静刘俏彭六保易利丹阳巧凤曾小慧中南大学湘雅二医院药学部湖南长沙410011 中南大学药学院湖南长沙410013

romidepsin是一种新的组蛋白去乙酰化酶抑制剂,可引起组蛋白超乙酰化,使细胞周期停滞,造成某些肿瘤细胞株程序性凋亡。在美国该药已被批准用于治疗先前曾接受过至少1种系统治疗的皮肤T细胞淋巴瘤患者。本文从romidepsin的研发背景、药... 详细信息

romidepsin是一种新的组蛋白去乙酰化酶抑制剂,可引起组蛋白超乙酰化,使细胞周期停滞,造成某些肿瘤细胞株程序性凋亡。在美国该药已被批准用于治疗先前曾接受过至少1种系统治疗的皮肤T细胞淋巴瘤患者。本文从romidepsin的研发背景、药理学、临床研究以及安全性评价等方面进行系统的概述,以推动romidepsin的进一步应用和研究。

关键词： romidepsin 淋巴瘤,T细胞,皮肤组蛋白去乙酰酶抑制剂药理学,临床

romidepsin促进靶向NKG2DL-CAR-T细胞对卵巢癌细胞的杀伤作用实验研究

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Romidepsin促进靶向NKG2DL-CAR-T细胞对卵巢癌细胞的杀伤作用实验...

组蛋白去乙酰化酶抑制剂romidepsin在美国获准用于治疗皮肤T细胞淋巴瘤

2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者：王亮余丽蕊福建省妇产医院

背景:为了提高嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)在治疗以卵巢癌为代表的实体瘤中的效果,希望促进肿瘤细胞靶抗原上调,提高CAR-T的cytotoxicity.材料与方法:以卵巢癌细胞表面NKG2D配体为靶抗原,构建NKG2D-CAR-... 详细信息

背景:为了提高嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)在治疗以卵巢癌为代表的实体瘤中的效果,希望促进肿瘤细胞靶抗原上调,提高CAR-T的cytotoxicity.材料与方法:以卵巢癌细胞表面NKG2D配体为靶抗原,构建NKG2D-CAR-T细胞,创新性联合romidepsin处理卵巢癌细胞SKOV3,探究SKOV3表面NKG2DL的表达改变,并采用LDH释放试验验证CAR-T细胞的细胞杀伤作用,利用ELISA方法确定细胞因子的分泌。结果:流式细胞术结果显示靶向NKG2DL-CAR-T细胞得到有效活化,romidepsin处理导致SKOV3表面NKG2DL表达增强;细胞毒性实验显示romidepsin通过调控卵巢癌细胞NKG2DL表达增强从而提高NKG2D-CAR-T细胞的对卵巢癌的杀伤能力(P<0.05);IFN-γ的分泌与杀伤作用同步升高(P<0.05),IL-2、PFP在较低效靶比时存在统计学意义,而PD-1并未受到影响(P≥0.05)。结论:通过增强肿瘤细胞靶抗原的表达是解决CAR-T细胞在实体瘤上应用不佳的方法。

关键词： CAR-T细胞卵巢癌 NKG2DL romidepsin 细胞杀伤

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药学进展 2010年第4期34卷 191-191页

Gloucester制药公司开发的组蛋白去乙酰化酶(HDAC)抑制剂romidepsin(商品名:Istodax)最近在美国获准用于先前至少接受过一种全身性治疗的罕见癌症--皮肤T细胞淋巴瘤(CTCL)患者,它是继默克公司开发的CTCL治疗药vorinostat之后在美国获准... 详细信息

Gloucester制药公司开发的组蛋白去乙酰化酶(HDAC)抑制剂romidepsin(商品名:Istodax)最近在美国获准用于先前至少接受过一种全身性治疗的罕见癌症--皮肤T细胞淋巴瘤(CTCL)患者,它是继默克公司开发的CTCL治疗药vorinostat之后在美国获准上市的第2个HDAC抑制剂,后者是用于在接受两种其他全身性治疗的同时或之后的进行性、持续性、复发性CTCL患者.Gloucester制药公司CEO Alan Colowick称,'Istodax的获准对公司和患者都有重大意义,为该产品用于肿瘤治疗的进一步临床开发迈出了重要一步,我们期待于2010年获得本品用于外周T细胞淋巴瘤(PTCL)的临床研究数据,并继续开发本品用于血液系统肿瘤和实体瘤.'

关键词： romidepsin 组蛋白去乙酰化酶抑制剂皮肤T细胞淋巴瘤

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of Hepatic Surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model romidepsin EGFR Liver cancer