Delving into the Latest Updates on Thioridazine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

10-[2-(1-methyl-2-piperidyl)ethyl]-2-methylsulfanyl-phenothiazine, 2-Methylmercapto-10-(2-(N-methyl-2-piperidyl)ethyl)phenothiazine, 3-Methylmercapto-N-(2'-(N-methyl-2-piperidyl)ethyl)phenothiazine

+ [7]

Target

5-HT2A receptor x D1 receptor x D2 receptor x hERG x α1A-AR x α1B-AR

Mechanism

5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), D1 receptor antagonists(Dopamine D1 receptor antagonists), D2 receptor antagonists(Dopamine D2 receptor antagonists)

+ [3]

Therapeutic Areas

NeoplasmsDigestive System DisordersImmune System Diseases+ [1]

Active Indication

Hepatocellular CarcinomaDiffuse Large B-Cell Lymphoma

Inactive Indication

Generalized anxiety disorderSchizophrenia

Originator Organization

Novartis Pharma AG

Active Organization

Beijing Sopuxingda Pharmaceutical Research Co., Ltd.

Helmholtz Zentrum München

Inactive Organization

Novartis Pharmaceuticals Corp.

Drug Highest PhasePhase 3

First Approval Date

US (18 Oct 1978),

Generalized anxiety disorderSchizophrenia

Regulation-

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Structure

Molecular FormulaC21H26N2S2

InChIKeyKLBQZWRITKRQQV-UHFFFAOYSA-N

CAS Registry50-52-2

To preliminarily explore the effectiveness of TP21 in TACE treatment of hepatocellular carcinoma. Using epirubicin hydrochloride as a control, compare the efficacy of TP21 or TP21 combined with epirubicin hydrochloride in TACE treatment of hepatocellular carcinoma. Secondary purpose: To evaluate the safety of TP21 in TACE treatment of hepatocellular carcinoma.

Start Date15 Mar 2019

Sponsor / Collaborator

Beijing Sopuxingda Pharmaceutical Research Co., Ltd.

[+1]

NCT02600741 / CompletedNot Applicable

A 12-Month Randomized, Open-Label Study of Caregiver Psycho-education and Skills Training in Patients Recently Diagnosed With Schizophrenia, Schizoaffective Disorder, or Schizophreniform Disorder and Receiving Paliperidone Palmitate or Oral Antipsychotic Treatment

The primary purpose of this study is to evaluate the overall effect of caregivers receiving a study-provided caregiver psycho-education and skills training program on the number of treatment failures (psychiatric hospitalization, psychiatric emergency room (ER) visit, crisis center visit, mobile crisis unit intervention, arrest/incarceration, and suicide or suicide attempt) in patients under their care during a 12 month period.

Start Date24 Jul 2015

Sponsor / Collaborator

Janssen Scientific Affairs LLC

100 Clinical Results associated with Thioridazine

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100 Translational Medicine associated with Thioridazine

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100 Patents (Medical) associated with Thioridazine

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2,317

Literatures (Medical) associated with Thioridazine

01 Oct 2024·International Journal for Parasitology

Acanthamoeba castellanii trophozoites need oxygen for normal functioning and lipids are their preferred substrate, offering new possibilities for treatment

Article

Author: Brouwers, Jos F. ; Mykytyn, Anna Z. ; Mykytyn, Anna Z ; Sarink, Maarten J ; Jedidi, Aïsha ; Houweling, Martin ; Sarink, Maarten J. ; Brouwers, Jos F ; Tielens, Aloysius G M ; G. M. Tielens, Aloysius ; van Hellemond, Jaap J ; van Hellemond, Jaap.J. ; Ruijter, George ; Verbon, Annelies

Acanthamoebae, pathogenic free-living amoebae, can cause Granulomatous Amoebic Encephalitis (GAE) and keratitis, and for both types of infection, no adequate treatment options are available. As the metabolism of pathogens is an attractive treatment target, we set out to examine the energy metabolism of Acanthamoeba castellanii and studied the aerobic and anaerobic capacities of the trophozoites. Under anaerobic conditions, or in the presence of inhibitors of the electron-transport chain, A. castellanii trophozoites became rounded, moved sluggishly and stopped multiplying. This demonstrates that oxygen and the respiratory chain are essential for movement and replication. Furthermore, the simultaneous activities of both terminal oxidases, cytochrome c oxidase and the plant-like alternative oxidase, are essential for normal functioning and replication. The inhibition of normal function caused by the inactivity of the respiratory chain was reversible. Once respiration was made possible again, the rounded, rather inactive amoebae formed acanthopodia within 4 h and resumed moving, feeding and multiplying. Experiments with radiolabelled nutrients revealed a preference for lipids over glucose and amino acids as food. Subsequent experiments showed that adding lipids to a standard culture medium of trophozoites strongly increased the growth rate. Acanthamoeba castellanii trophozoites have a strictly aerobic energy metabolism and β-oxidation of fatty acids, the Krebs cycle, and an aerobic electron-transport chain coupled to the ATP synthase, producing most of the used ATP. The preference for lipids can be exploited, as we show that three known inhibitors of lipid oxidation strongly inhibited the growth of A. castellanii. In particular, thioridazine and perhexiline showed potent effects in low micromolar concentrations. Therefore, this study revealed a new drug target with possibly new options to treat Acanthamoeba infections.

06 Aug 2024·ACS Nano

Stimuli-Responsive Hydrogels Potentiating Photothermal Therapy against Cancer Stem Cell–Induced Breast Cancer Metastasis

Article

Author: Tang, Ben Zhong ; Ning, Shipeng ; Ping, Wei ; Zhang, Ni ; Zhang, Tianfu ; Chen, Jingqi ; Huang, Rong ; Suo, Meng ; Pan, You ; Lyu, Meng

The self-renewal and differentiation properties of cancer stem cells (CSCs) result in chemoresistance in breast cancer. Even though numerous drugs have been developed to target CSCs, they have suffered from inefficient delivery and accumulation at the focal site. Here, a thermoresponsive hydrogel is developed by coencapsulating aggregation-induced emission (AIE)-active photothermal agent and thioridazine (THZ), demonstrating a controllable delivery system triggered by the AIE agent to augment THZ-mediated CSC ablation. Upon near-infrared laser stimuli, the photothermal effect from the AIE agent induces hydrogel deformation for burst drug release. The precise in situ tumor administration of the hydrogel accelerates drug diffusion and accumulation in deep breast cancer lesions. Thus, THZ can invade tumors and provoke massive CSC apoptosis via dopamine receptor blockage and oxidative stress induction. Consequently, effective CSC inhibition and significant suppression of tumor recurrence and metastasis are demonstrated in mice with breast cancer. We believe that this intelligent hydrogel-based delivery system represents a promising treatment strategy for metastatic breast cancer with clinical potential.

01 Aug 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Identification of host antioxidant effectors as thioridazine targets: Impact on cardiomyocytes infection and Trypanosoma cruzi-induced acute myocarditis

Article

Author: Caetano-da-Silva, José Edson ; Vilela Gonçalves, Reggiani ; Gonçalves-Santos, Elda ; Cardoso Santos, Eliziária ; Liz Belli Cassa Domingues, Elisa ; Mól Pelinsari, Silvania ; Dias Novaes, Rômulo ; Santana Caldas, Ivo ; Figueiredo Diniz, Lívia

Phenothiazines inhibit antioxidant enzymes in trypanosomatids. However, potential interferences with host cell antioxidant defenses are central concerns in using these drugs to treat Trypanosoma cruzi-induced infectious myocarditis. Thus, the interaction of thioridazine (TDZ) with T. cruzi and cardiomyocytes antioxidant enzymes, and its impact on cardiomyocytes and cardiac infection was investigated in vitro and in vivo. Cardiomyocytes and trypomastigotes in culture, and mice treated with TDZ and benznidazole (Bz, reference antiparasitic drug) were submitted to microstructural, biochemical and molecular analyses. TDZ was more cytotoxic and less selective against T. cruzi than Bz in vitro. TDZ-pretreated cardiomyocytes developed increased infection rate, reactive oxygen species (ROS) production, lipid and protein oxidation; similar catalase (CAT) and superoxide dismutase (SOD) activity, and reduced glutathione's (peroxidase - GPx, S-transferase - GST, and reductase - GR) activity than infected untreated cells. TDZ attenuated trypanothione reductase activity in T. cruzi, and protein antioxidant capacity in cardiomyocytes, making these cells more susceptible to H₂O₂-based oxidative challenge. In vivo, TDZ potentiated heart parasitism, total ROS production, myocarditis, lipid and protein oxidation; as well as reduced GPx, GR, and GST activities compared to untreated mice. Benznidazole decreased heart parasitism, total ROS production, heart inflammation, lipid and protein oxidation in T. cruzi-infected mice. Our findings indicate that TDZ simultaneously interact with enzymatic antioxidant targets in cardiomyocytes and T. cruzi, potentiating the infection by inducing antioxidant fragility and increasing cardiomyocytes and heart susceptibility to parasitism, inflammation and oxidative damage.

100 Deals associated with Thioridazine

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External Link

KEGG	Wiki	ATC	Drug Bank
D00373	Thioridazine	N05AC02	DB00679

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 3	CN	Beijing Sopuxingda Pharmaceutical Research Co., Ltd.	29 Aug 2022
Diffuse Large B-Cell Lymphoma	Preclinical	DE	Helmholtz Zentrum München	01 Dec 2012