Delving into the Latest Updates on Miriplatin Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

DACHPM, DACHPt(II)(Myr)2, Miriplatin

+ [7]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors), DNA cross linking agents

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Hepatocellular Carcinoma

Inactive Indication-

Originator Organization

Sumitomo Pharma Co., Ltd.

Active Organization

Sumitomo Pharma Co., Ltd.

Inactive Organization

SSY Group Ltd.

Drug Highest PhaseApproved

First Approval Date

JP (16 Oct 2009),

Hepatocellular Carcinoma

Regulation-

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Structure/Sequence

Molecular FormulaC34H70N2O5Pt

InChIKeyLWDBMUAJGMXQAY-GSEQGPDBSA-L

CAS Registry250159-48-9

View All Structures (2)

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.

01 Jun 2023·Biochemical Pharmacology

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

Article

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

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.

01 Mar 2022·Interventional Radiology

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

Article

Author: 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 Deals associated with Miriplatin Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D06294	Miriplatin Hydrate	L01XX	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatocellular Carcinoma	JP	Sumitomo Pharma Co., Ltd.	16 Oct 2009

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	CN	SSY Group Ltd.	31 Dec 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2009	Phase 2	Hepatocellular Carcinoma	126	SM-11355	enmxybcnwp(qbgeiuxfsu) = zrgkljkuay khxwariscf (cztvdqowtg ) View more	-	20 May 2009
				Zinostatin stimalamer	enmxybcnwp(qbgeiuxfsu) = ktyvpqmsuj khxwariscf (cztvdqowtg ) View more