Phase II Study to evaluate the efficacy and safety of bioadhesive barrier-forming oral liquid gel (Episil) for prevention of oral mucositis in patients who are receiving chemotherapy (In DFP therapy of esophageal cancer)

开始日期2022-05-30

申办/合作机构-

NCT02198508

/ CompletedN/AIIT

The Shuttle Effect : Combination Therapy With Deferiprone and Deferasirox in Transfusion-dependent Thalassemia Patients.

Background: Three iron chelators now available on the market differ in toxicity and organ specificity; evidence on standardized chelation protocol remains inconclusive, but patients with transfusion-dependent beta-thalassemia treated with DFO infusion show significant differences in the limitations of daily activities, physical activity, and quality of life when treated with oral chelator. With licensing of DFP in America, it is reasonable to combine DFP with DFX. Patients find two oral chelators more acceptable than one oral and one injectable. This pilot study rates use of DFP for improving iron excretion profile of deferasirox.
Methods: The investigators enrolled 13 beta-thalassemia patients in China Medical University Children's Hospital in May 2009-October 2011. Five refused to take part in pharmacokinetics; they only participated in iron excretion study. Seven with irregular bowel function were unable to collect feces in the screening period as baseline data. Subjects were randomly assigned and rotated to undergo all treatments (with informed consent): (A) single oral dose of DFX 30 mg/kg once daily, (B) single oral dose of DFP 40 mg/kg twice a day, (C) oral doses of DFX and DFP administered sequentially (DFX 30 mg/kg/d, deferiprone 40 mg/kg/d and deferiprone 40 mg/kg/d at 7-hour intervals). Three-day drug dosage was followed by four-day washout. Collections of urine and stool proceeded 24 hours per day, each analyzed separately. Through a venous catheter, serial blood samples (1 mL/each sampling) were collected in glass tubes containing heparin as anticoagulant at Time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dose; plasma concentrations of DFP and DFX were measured.

开始日期2007-07-01

申办/合作机构

中国医药大学附设医院

NCT00733811

/ Completed临床4期IIT

Phase IV Study of the Use of Sequential DFP-DFO Versus DFP in Thalassemia Major Patients

Changes in chelation treatment and transfusion practices, during the past two decades, have dramatically improved the prognosis of thalassemia major patients.Deferiprone (DFP) has been compared with deferoxamine (DFO), using different schedules of treatment, in the majority of the 13 clinical trials published between 1990 and 2008.No statistically significant difference was shown between these two interventions during, at most, 18 months of treatment.Three randomised trials that compared sequential DFP-DFO treatment versus DFO alone reported controversial results but this could be due to small sample sizes and short treatment duration. In fact, no trial with treatment duration longer than 18 months15, which reported on mortality, adverse events, serum ferritin concentrations, as well as costs has so far been published.
This long-term sequential DFP-DFO treatment versus DFP alone treatment trial was conducted to assess the impacts of these chelation treatments on serum ferritin concentrations, mortality, adverse events, and costs in thalassemia major patients.

开始日期2000-09-01

申办/合作机构-

100 项与异氟磷相关的临床结果

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100 项与异氟磷相关的转化医学

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100 项与异氟磷相关的专利（医药）

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3,324

项与异氟磷相关的文献（医药）

2026-06-01·FREE RADICAL BIOLOGY AND MEDICINE

Deferiprone mitigates imidacloprid-induced neurotoxicity: Roles of iron chelation, ferroptosis, and ferritinophagy

Article

作者: Hindelah, Youssef G ; Ghaiad, Heba R ; Motawi, Tarek K

Imidacloprid (IMI) is a commonly used chloronicotinyl insecticide, although it has low specificity to humans, long-term exposure would induce neurotoxicity through cholinergic signaling disruption and ferroptosis activation. The current investigation aimed to explore the neuroprotective impact of deferiprone (DFP), an iron chelator, against IMI-induced neurotoxicity and whether co-administration with everolimus (EVR), an mTOR inhibitor known to induce autophagy and potentially enhance ferritinophagy, would alter this effect. Adult male Wistar rats were assigned randomly to four different experimental sets: control, IMI, IMI + DFP, and IMI + DFP + EVR groups. They were given IMI (90 mg/kg/day, p.o.), DFP (125 mg/kg/day, p.o.), and EVR (1 mg/kg/day, i.p.) for 30 days. Rats were subjected to neurobehavioral assessments including open-field, rotarod, Y-maze, and tail-immersion tests. Rats' cortices were examined histologically, and acetylcholinesterase (AChE) expression was evaluated immunohistochemically. Several biochemical markers were assessed including oxidative stress markers such as reduced and oxidized glutathione, superoxide dismutase and malondialdehyde, in addition to ferroptotic markers including acyl-CoA synthetase long-chain family member-4, lysophosphatidylcholine acyltransferase-3, iron responsive element binding protein-2, ferritin heavy chain-1, and transferrin receptor-1. IMI administration led to marked biochemical derangements, cortical damage, reduced AChE expression, altered spontaneous motor function, locomotor coordination, spatial memory, and pain threshold while increasing anxious behaviours. DFP ameliorated oxidative stress, reduced ferroptotic markers and alleviated the neurobehavioural defects. Meanwhile, co-administration of EVR abolished these protective effects, consistent with enhanced autophagy-associated iron release and ferroptosis activation. Overall, these findings support the therapeutic potential of DFP against IMI-induced neurotoxicity and highlight ferroptosis as a promising therapeutic target in pesticide-related neurodegeneration.

2026-05-12·ACS Omega

Transcriptomic Signature and PROTAC Strategy Revealed Histone Lysine Demethylase as a Target of Anticancer Activity of Deferiprone

Article

作者: Murugan, Janani ; Walunj, Dipak ; Oyelere, Adegboyega K. ; Kern, Ryan ; Johnston, Alexis ; Clarke, Brandon J. ; Hathaway, Nathaniel A. ; Olugbami, Jeremiah O. ; Bangaru, Arvind ; Yang, Ruiqiao ; Wu, Bocheng ; Fan, Yuhong ; Nelson, Travis J.

Deferiprone (DFP) is an iron chelator approved for treating iron overload in thalassemia patients. Recent observations have suggested that DFP has promising anticancer activities ascribed to several mechanisms, including reduction of the intracellular free labile iron and zinc ion pools and inhibition of the activities of other intracellular targets, including ribonucleotide reductase (RNR). We previously reported that DFP inhibits the demethylase activities of several Fe-(II)/α-ketoglutarate-dependent histone lysine demethylases (KDMs) at much lower concentrations, at which it inhibits RNR activities and/or reduces the labile intracellular iron and zinc ion pools. In this study, we used RNA sequencing (RNA seq) and PROTACs strategies to validate and quantify the contribution of intracellular KDM inhibition to the antiproliferative activities of DFP. We report herein that DFP elicited a gene expression signature that is largely similar to that of JIB-04, an established KDM inhibitor (KDMi), in two breast cancer (BCa) cells (MCF-7 and MDA-MD-231). Importantly, RNA seq revealed that DFP and JIB-04 downregulated the expression of hypoxia-inducible factor 1α (HIF-1α), an oncogene whose expression is commonly modulated through histone demethylation mediated by KDMs and degraded by several KDMi. Moreover, DFP-derived PROTACs elicited enhanced cancer cell-selective antiproliferative activities and intracellular on-target effects, downregulating several KDMs implicated in the etiology of BCa cells, including a strong degradation of KDMs 2A, 3A, and 5B, and a moderate degradation of KDMs 4A-C, 5C, and 6B. Collectively, our data support KDM inhibition as a key mechanism of anticancer activity of DFP and identify that PROTAC is a viable strategy to obtain novel DFP analogs with improved potency and therapeutic index.

2026-05-01·Brain, behavior, & immunity - health

Multi-omic analysis reveals brain–blood concordance and persistent neuroimmune reprogramming with stress and toxicant exposure in a mouse model of Gulf War Illness

Article

作者: Michalovicz, L T ; O'Callaghan, J P ; Sasaki, A ; Ashbrook, D G ; Kelly, K A ; McGowan, P O ; Wijenayake, S

Gulf War Illness (GWI) is a chronic neuroimmune condition affecting veterans of the 1990-91 Gulf War. Current treatments primarily target symptom relief, and the biological mechanisms underlying GWI remain poorly understood. Using a validated mouse model of Gulf War Illness (GWI) combining corticosterone (CORT) and diisopropyl fluorophosphate (DFP) exposure to induce stress- and toxicant-related neuroimmune priming, we examined how prior exposure alters molecular responses to a subsequent immune challenge. Male mice were exposed to CORT and DFP with repeated intermittent CORT, followed by lipopolysaccharide (LPS) or saline to assess transcriptional and epigenetic changes in brain and blood. We analysed transcript abundance, chromatin accessibility, and DNA methylation in the hippocampus, frontal cortex, and blood at 6 h, 12 h and 24hrs after LPS challenge (3-4 mice per group). We identified widespread transcriptional changes and dynamic chromatin accessibility following LPS exposure, with DNA methylation modifications that persisted in the hippocampus and blood. Thirty-three genes, including Stat3, Plpp3, Cdkn1a, and Fgfr2, were differentially expressed and methylated in both hippocampus and blood across all time points. These genes clustered in immune- and glial-related pathways. Transcription factor analysis revealed enrichment of NF-κB, CREB1, EGR1, JUN, and MYC binding motifs in regions with differential methylation. Our findings identify novel candidate biomarkers in peripheral blood that reflect brain molecular changes, providing a new framework for elucidating the long-term epigenetic impacts of stress and toxicant exposure in GWI.

100 项与异氟磷相关的药物交易

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