米铂水合物(Miriplatin Hydrate) - 药物靶点：DNA_在研适应症：肝细胞癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

DACHPM、DACHPt(II)(Myr)2、Miriplatin

+ [7]

靶点

DNA

作用机制

DNA抑制剂(DNA抑制剂)、DNA交联剂、DNA合成抑制剂

治疗领域

肿瘤消化系统疾病

在研适应症

肝细胞癌

非在研适应症-

原研机构

Sumitomo Pharma Co., Ltd.

在研机构

Sumitomo Pharma Co., Ltd.

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (2009-10-16),

肝细胞癌

最高研发阶段(中国)-

特殊审评-

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结构

分子式C34H70N2O5Pt

InChIKeyLWDBMUAJGMXQAY-GSEQGPDBSA-L

CAS号250159-48-9

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关联

29

项与米铂水合物相关的临床试验

CTR20171501 / Terminated临床3期

以盐酸表柔比星为对照评价注射用米铂治疗肝细胞癌的有效性和安全性的随机开放平行对照多中心临床试验

以盐酸表柔比星为对照，评估注射用米铂治疗肝细胞癌的有效性和安全性

开始日期2018-04-24

申办/合作机构

江苏奥赛康药业有限公司

JPRN-UMIN000029504 / Suspended临床2期IIT

Balloon occluded transarterial chemoembolization using miriplatin in HCC: A Multicenter, Clinical Phase II study - B-TACE study

开始日期2017-10-26

申办/合作机构-

JPRN-jRCTs031180365 / CompletedN/AIIT

Efficacy and safety of transcatheter arterial chemoembolization with warmed miriplatin for unresectable hepatocellular carcinoma - Miriplatin TACE study

开始日期2017-06-27

申办/合作机构-

100 项与米铂水合物相关的临床结果

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100 项与米铂水合物相关的转化医学

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100 项与米铂水合物相关的专利（医药）

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90

项与米铂水合物相关的文献（医药）

2023-11-01·Acta Pharmaceutica Sinica B

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

Article

作者: Shao, Rongguang ; Wang, Mengyan ; Zhao, Wuli ; Xia, Guimin ; Cai, Meilian ; Wang, Xiaowei

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

2023-06-01·Biochemical Pharmacology

Enhanced binding of β-catenin and β-TrCP mediates LMPt’s anti-CSCs activity in colorectal cancer

Article

作者: Zhao, Wenxia ; Zhao, Wuli ; Zhou, Huimin ; Zhang, Yefan ; Wang, Kexin ; Xi, Xiaoming ; Wang, Mengyan ; Shao, Rongguang ; Cai, Meilian ; Zhao, Cong ; Li, Yang ; Wang, Xiaowei ; Xia, Guimin

Cancer stem cells (CSCs), a subpopulation of tumor cells with the features of self-renewal, tumor initiation, and insensitivity to common phys. and chem. agents, are the key to cancer relapses, metastasis, and resistance.Accessible CSCs inhibitory strategies are primarily based on small mol. drugs, yet toxicity limits their application.Here, we report a liposome loaded with low toxicity and high effectiveness of miriplatin, lipo-miriplatin (LMPt) with high miriplatin loading, and robust stability, exhibiting a superior inhibitory effect on CSCs and non-CSCs.LMPt predominantly inhibits the survival of oxaliplatin-resistant (OXA-resistant) cells composed of CSCs.Furthermore, LMPt directly blocks stemness features of self-renewal, tumor initiation, unlimited proliferation, metastasis, and insensitivity.In mechanistic exploration, RNA sequencing (RNA-seq) revealed that LMPt downregulates the levels of pro-stemness proteins and that the β-catenin-mediated stemness pathway is enriched.Further research shows that either in adherent cells or 3D-spheres, the β-catenin-OCT4/NANOG axis, the vital pathway to maintain stemness, is depressed by LMPt.The consecutive activation of the β-catenin pathway induced by mutant β-catenin (S33Y) and OCT4/NANOG overexpression restores LMPt's anti-CSCs effect, elucidating the key role of the β-catenin-OCT4/NANOG axis.Further studies revealed that the strengthened binding of β-catenin and β-TrCP initiates ubiquitination and degradation of β-catenin induced by LMPt.In addition, the ApcMin/+ transgenic mouse model, in which colon tumors are spontaneously formed, demonstrates LMPt's potent anti-non-CSCs activity in vivo.

2022-03-01·Interventional Radiology

Combination Therapy by Transarterial Injection of Miriplatin-Iodized Oil Suspension with Microwave Ablation for Medium-Sized Hepatocellular Carcinoma: the Preliminary Experience

Article

作者: Kinota, Naoya ; Fujii, Takaaki ; Kato, Hirotaka ; Kudo, Kyohei ; Miyamoto, Noriyuki ; Kanaya, Motoma

PurposeTo evaluate the feasibility and safety of transarterial injection of a miriplatin-iodized oil suspension combined with Emprint miriplatin-iodized oil suspension-microwave ablation in patients with medium-sized (3-5 cm) hepatocellular carcinomas.Materials and MethodsThis retrospective study included a total of 11 patients with 12 hepatocellular carcinomas (mean size, 3.6 ± 0.6 cm) underwent miriplatin-iodized oil suspension-microwave ablation. Microwave ablation was performed under the guidance of computed tomography fluoroscopy following transarterial miriplatin-iodized oil suspension injection on the same day. Technical success, complications, and local tumor progression were assessed.ResultsThe primary and secondary technical success rates were 75.0% and 100%, respectively. The number of treatment sessions per nodule was 1.25 ± 0.45. A total 15 sessions were required to achieve technical success (one session in nine lesions, two sessions in three lesions). Two major complications (pneumothorax [n = 1] and hemorrhage [n = 1]) occurred (2/15, 13.3%). No local tumor progression was observed during the follow-up period (mean 12.0 ± 2.0 months, range 2.7-23.9 months).ConclusionsMiriplatin-iodized oil suspension-microwave ablation for medium-sized hepatocellular carcinomas can be safely performed with good local control.

100 项与米铂水合物相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06294	米铂水合物	L01XX	-

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
肝细胞癌	日本	Sumitomo Pharma Co., Ltd.	2009-10-16

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临床结果

适应症

分期

评价

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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	肝细胞癌	126	SM-11355	醖構網膚鹹糧蓋壓餘鏇(鬱製醖艱夢夢鏇製範窪) = 窪鹽廠淵觸構齋鹽遞顧憲鬱構廠窪簾衊鹹鹹構 (鏇壓餘蓋獵鏇築顧淵夢 ) 更多	-	2009-05-20
				Zinostatin stimalamer	醖構網膚鹹糧蓋壓餘鏇(鬱製醖艱夢夢鏇製範窪) = 獵繭獵鏇鏇鬱鑰餘鏇繭憲鬱構廠窪簾衊鹹鹹構 (鏇壓餘蓋獵鏇築顧淵夢 ) 更多