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

Action

inhibitors

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.

License Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (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)

ABSTRACTWithin the current challenges in medicinal chemistry, the creation of novel and improved therapeutic agents stands out. 2‐Cyano‐3‐(thiophen‐2‐yl)prop‐2‐enethioamide (CTPTA) ligand was complexed with palladium (II) and platinum (II) ions within the nanoscale with the molecular formula [M (CTPTA)Cl2]. H2O. The CTPTA ligand and its complexes were characterized by elemental analysis, UV–Vis spectra, FTIR, mass spectra, TGA, magnetic measurement, and the molar conductance technique. Analysis with a scanning electron microscope (SEM) revealed that the nanostructure dimension of both complexes is predominantly between 10 and 30 nm. The CTPTA ligand functions as a bidentate ligand, utilizing thione sulfur, and cyanide nitrogen atoms. Density functional theory was employed to analyze the geometric structure properties of the CTPTA ligand and its complexes. Natural population (NPA) and Mulliken population (MPA) methods were used to calculate the charge distribution. The cytotoxic impact results of all compounds on human liver cancer (HepG2) cell line were satisfactory. The ligand and its complexes were also tested against gram‐negative and gram‐positive bacteria in vitro. The findings of the molecular docking study supported the cytotoxicity and antibacterial effects. The antioxidant and anti‐inflammation activities of synthesized palladium (II) and platinum (II) complexes had a great spectrum of activity. The preclinical pharmacokinetic studies on albino rats revealed that the newly studied complexes achieved excellent antitumor results. This was clear in the investigated parameters, especially the amelioration of AFP levels, liver weight, oxidative stress, and lobular hepatic architecture injury.

01 Oct 2024·International Journal of Biological Macromolecules

Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions

Article

Author: Costa, Luiz Antônio S ; Ferreira, Frederico Henrique do C ; Farrell, Nicholas P

In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed. Especially, changes in structural parameters suggesting condensation and reduction of available surface area will reduce or prevent normal protein recognition and may thus potentially inhibit biological mechanisms related to apoptosis (DNA) or reduced vascularization viability (HEP). Thermodynamic analyses supported these findings with favourable interaction energies. The comparison of DNA and heparin confirms the general intersectionality between the two biomolecules and confirms the intrinsic dual-nature function of this chemotype. The distinction between the two-limiting mode of actions (HS or DNA-centred) could reflect an intriguing balance between extracellular (GAG) and intracellular (DNA) binding and affinities. The results underline the need to fully understand GAG-small molecule interactions and their contribution to drug pharmacology and related therapeutic modalities. This report contributes to that understanding.

01 Oct 2024·European Journal of Pharmaceutics and Biopharmaceutics

Metal complex lipid-based nanoparticles deliver metabolism-regulating lomitapide to overcome CTC immune evasion via activating STING pathway

Article

Author: Miao, Lin ; Chen, Liqing ; Wang, Ping ; Fan, Ni ; Gao, Zhonggao ; Zhao, Feng ; Tang, Manqing ; Li, Yingpeng ; Wu, Xuanjun ; Meng, Yuanyuan ; Li, Yunfei

Activating the cGAS-STING pathway of circulating tumor cell clusters (CTC clusters) represents a promising strategy to mitigate metastases. To fully exploit the potential of cholesterol-regulating agents in activating CTCs' STING levels, we developed a nanoparticle (NP) composed of metal complex lipid (MCL). This design includes MCL-miriplatin to increase NP stiffness and loads lomitapide (lomi) modulating cholesterol levels, resulting in the creation of PLTs@Pt-lipid@lomi NPs. MCL-miriplatin not only enhances lomi's eliciting efficacy on STING pathway but also increases NPs' stiffness, thus a vital factor affecting the penetration into CTC clusters to further boost lomi's ability. Demonstrated by cy5 tracking experiments, PLTs@Pt-lipid@lomi NPs quickly attach to cancer cell via platelet membrane anchorage, penetrate deep into the spheres, and reach the subcellular endoplasmic reticulum where lomi regulates cholesterol. Additionally, these NPs have been shown to track CTCs in the bloodstream, a capability not demonstrated by the free drug. PLTs@Pt-lipid@lomi NPs more efficiently activate the STING pathway and reduce CTC stemness compared to free lomi. Ultimately, PLTs@Pt-lipid@lomi NPs reduce metastasis in a post-surgery animal model. While cholesterol-regulating agents are limited in efficacy when being repositioned as immunomodulatory agents, this MCL-composing NP strategy demonstrates the potential to effectively deliver these agents to target CTC clusters.

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	Japan	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 1	China	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	ibznjfvpvu(sasngbemow) = rapigpebgn xjagxgxnyl (qujbptleqo ) View more	-	20 May 2009
				Zinostatin stimalamer	ibznjfvpvu(sasngbemow) = pgidbnvbfh xjagxgxnyl (qujbptleqo ) View more