Delving into the Latest Updates on Ferric ammonium citrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Ferric ammonium citrate (JAN/USP), Ferric ammonium citrate, green

+ [3]

Target-

Mechanism

Fe modulators

Therapeutic Areas

Digestive System DisordersEndocrinology and Metabolic DiseaseHemic and Lymphatic Diseases

Active Indication

Gastrointestinal DiseasesAnemia, Iron-Deficiency

Inactive Indication

Chronic Kidney DiseasesHyperphosphatemiaKidney Failure, Chronic

Originator Organization

Otsuka Pharmaceutical Co., Ltd.

Active Organization

Otsuka Pharmaceutical Co., Ltd.

Hunan Hansen Pharmaceutical Co. Ltd.

Inactive Organization

Sinomune Pharmaceutical Co., Ltd.

Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.

Panion & BF Biotech, Inc.

+ [2]

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1982),

Anemia, Iron-Deficiency

Regulation-

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Structure

Molecular FormulaC6H11FeNO7

InChIKeyPLKYGPRDCKGEJH-UHFFFAOYSA-N

CAS Registry1185-57-5

Iron death is a novel type of programmed cell death caused by excessive accumulation of iron-dependent lipid peroxidation products; however, the function of iron death during porcine oocyte maturation and embryo growth is poorly understood. This study was conducted to investigate the mechanism of ferric ammonium citrate (FAC) in regulating iron death in mature oocytes in vitro through the NRF2 signaling pathway, and subsequent embryonic development. The experiment was divided into four groups: 0 (control group), 2, 5, and 10 μM FAC. Western blotting (WB), reactive oxygen species (ROS)assays, mitochondrial membrane potential (MMP) assays, and Quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the maturation of porcine oocytes in vitro, the protein content of nuclear transcription factor E2-related factor 2 (Nrf2), the distribution of mitochondria, the level of oxidative stress, and the development of embryos fertilized in vitro. The results showed that with increasing FAC concentrations, the oocyte maturation rate in vitro, Nrf2 protein content, MMP, and cleavage rates of in vitro fertilized embryos decreased (significantly in the 5 μM group); the oxidative stress level was significantly increased; the transcript levels of Nrf2, GPX4, and FTH1 mRNAs were significantly decreased; the expression of ACSL4 was significantly upregulated (P < 0.05); and the blastocyst rate of embryos fertilized in vitro was reduced (significantly in the 2 μM group). In conclusion, FAC can regulate Nrf2 protein levels in porcine oocytes matured in vitro to induce iron death, affecting the maturation rate of oocytes, distribution of mitochondria, level of oxidative stress, expression of iron-death-related genes, and development of embryos after in vitro fertilization.

01 Dec 2024·International Immunopharmacology

Cardamonin attenuates iron overload-induced osteoblast oxidative stress through the HIF-1α/ROS pathway

Article

Author: Wang, Haibin ; Chen, Chuyi ; Wang, Fanchen ; Li, Shaocong ; Yang, Junzheng ; Lin, Yuewei ; He, Qi ; Meng, Kai ; Xiao, Jiacong ; Wang, Xintian ; Zeng, Jiaxu ; Li, Miao ; Chen, Bohao ; Chi, Weijin ; Pan, Zhaofeng ; Zhang, Hua ; Chen, Peng

BACKGROUNDOsteoporosis(OP) is a bone disease under research. Iron overload is a significant risk factor. Iron balance is crucial for bone metabolism and biochemical processes. When there is an excess of iron in the body, it tends to produce reactive oxygen species (ROS) which can cause oxidative damage to cells. The flavonoid compound, Cardamonin (CAR), possesses potent anti-inflammatory and anti-iron overload properties that can be beneficial in mitigating the risk of OP.PURPOSEThis study investigates the potential therapeutic interventions and underlying mechanisms of CAR for treating OP in individuals with iron overload.METHODSThe model of iron-overloaded mice was established by intraperitoneally injecting iron dextran(ID) into the mice. OP severity was evaluated with micro-CT and Hematoxylin-Eosin (HE) staining in vivo. In vitro, the iron-overloaded osteoblast model was induced by ferric ammonium citrate. Cell counting kit 8 assay to evaluate cell viability, Annexin V-FITC/PI assay to detect cell apoptosis. A range of cellular markers were detected, including the variation in mitochondrial membrane potential (MMP), levels of malondialdehyde (MDA), ROS, and lipid hydroperoxide (LPO).RESULTSCAR can reverse bone loss in iron overload-induced OP mouse models in vivo. CAR attenuates the impairment of iron overload on the activity and apoptosis of MC3T3-E1 cells as well as the accumulation of ROS and LPO activation via HIF-1α/ROS pathways.CONCLUSIONCAR downregulating HIF-1α pathways prevents inhibition of iron overload-induced osteoblasts dysfunctional by attenuating ROS accumulation, reducing oxidative stress, promotes bone formation, and alleviates OP.

01 Sep 2024·Cell Biochemistry and Biophysics

Iron Overload Induces Hepatic Ferroptosis and Insulin Resistance by Inhibiting the Jak2/stat3/slc7a11 Signaling Pathway

Article

Author: Pan, Ling ; Deng, Ling ; Liang, Min ; Liang, Yuzhen ; Xia, Ning ; Mo, Manqiu

Recent studies showed that patients with iron overload had increased risk of insulin resistance or diabetes. Ferroptosis is a new type of cell death mainly caused by iron-dependent oxidative damage. In the present study, we investigated potential mechanisms of iron overload induced hepatic ferroptosis and insulin resistance through in vivo and in vitro experiments. In vivo, the mice models of iron overload were established by intraperitoneal injection of iron dextran. The changes of body weight, serum ferritin and blood glucose were measured. Hematoxylin-eosin (HE) and Perl's stainings were used to observe the pathological changes and iron deposition in the liver of mice. In vitro, HepG2 cells were treated with ferric ammonium citrate (FAC, 9 mmol/L, 24 h) to establish the cell models of iron overload. The labile iron pool, cell viability, glucose consumption and glycogen contents were measured. The ultrastructure of mitochondria was observed by transmission electron microscope (TEM). The malondialdehyde (MDA) and glutathione (GSH) kits were used to detect lipid peroxidation in liver tissues of mice and HepG2 cells. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of ferroptosis factors and JAK2/STAT3 signaling pathway. In this study, we used the iron chelator deferasirox in mice and HepG2 cells. Iron overload caused weight loss, elevated serum ferritin, fasting blood glucose, fasting insulin, HOMA-IR, impaired glucose tolerance, and decreased insulin sensitivity in mice. HE staining and Perls staining showed clumps of iron deposition in the liver of iron overload mice. Iron overload could reduce the glucose consumption, increase MDA contents of HepG2 cells, while reduce glycogen and GSH contents in liver tissues of mice and HepG2 cells. TEM showed deletion of mitochondrial ridge and rupture of outer membrane in HepG2 cells with iron overload. Iron chelator deferasirox could significantly improve the above indicators, which might be related to the activation of JAK2/STAT3/SLC7A11 signaling pathway and hepatic ferroptosis. Iron overload could induce hepatic ferroptosis and insulin resistance by inhibiting the JAK2/STAT3/SLC7A11 signaling pathway, and the iron chelator deferasirox might improve hepatic insulin resistance induced by iron overload.

100 Deals associated with Ferric ammonium citrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D01644	Ferric ammonium citrate	V08CA07	DB09501

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Gastrointestinal Diseases	JP	Otsuka Pharmaceutical Co., Ltd.	02 Jul 1993
Anemia, Iron-Deficiency	CN	Hunan Hansen Pharmaceutical Co. Ltd.	01 Jan 1982

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperphosphatemia	Preclinical	CN	Jiangsu Carephar Pharmaceutical Co., Ltd.	09 Jun 2018
Hyperphosphatemia	Preclinical	CN	Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.	09 Jun 2018
Anemia	Discovery	CN	Panion & BF Biotech, Inc.	14 Oct 2020
Chronic Kidney Diseases	Discovery	CN	Panion & BF Biotech, Inc.	05 Aug 2019
Chronic Kidney Diseases	Discovery	CN	Choice Pharm Med Info Consultancy (Shanghai Co. Ltd.	05 Aug 2019
Kidney Failure, Chronic	Discovery	CN	Sinomune Pharmaceutical Co., Ltd.	24 May 2019
Hyperphosphatemia	Discovery	CN	Jiangsu Carephar Pharmaceutical Co., Ltd.	09 Jun 2018
Hyperphosphatemia	Discovery	CN	Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.	09 Jun 2018