General Information of the Drug (ID: ferrodrug0203)
Name
Ferric ammonium citrate
Synonyms
FERRIC AMMONIUM CITRATE; 1185-57-5; Ammonium iron(III) citrate; Ferric Ammonium Citrate, Brown; iron(3+) 2-hydroxypropane-1,2,3-tricarboxylate ammoniate; Ferriseltz (TN); 7050-19-3; Ammonium iron III citrate; Ammonium ferric citrate;FAC; SCHEMBL1920826; Ferric ammonium citrate (JAN/USP); AKOS015918211; D01644; E75831; J-003847; azane;2-hydroxypropane-1,2,3-tricarboxylate;iron(3+)

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Structure
3D MOL
Formula
C6H8FeNO7
IUPAC Name
azane;2-hydroxypropane-1,2,3-tricarboxylate;iron(3+)
Canonical SMILES
C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.N.[Fe+3]
InChI
InChI=1S/C6H8O7.Fe.H3N/c7-3(8)1-6(13,5(11)12)2-4(9)10;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;1H3/q;+3;/p-3
InChIKey
FRHBOQMZUOWXQL-UHFFFAOYSA-K
PubChem CID
14457
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Atherosclerosis ICD-11: BD40
Responsed Regulator NAD-dependent protein deacetylase sirtuin-1 (SIRT1) Suppressor
Pathway Response Autophagy hsa04140
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
A total of 20 male Apoe-/-mice (6-8 weeks of age, 18-22 g) were purchased from Charles River (Beijing, China). Mice were randomly assigned to a control group (normal diet: 4% fat, cholesterol free, and sodium cholate) and an AS group (high-fat diet: 20% fat, 1.25% cholesterol, and 0.5% sodium cholate).

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Response regulation Ferric ammonium citrate(FAC) can induce a decrease in foam cell activity rather than macrophage activity, increase lipid ROS levels, decrease GPX4 expression and inhibit SIRT1 expression. Activation of SIRT1 can inhibit the ferroptosis and IL-1 and IL-18 levels of foam cells in excess iron by autophagy, providing a novel therapeutic target for atherosclerosis(AS).
Unspecific Target
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Parkinson disease ICD-11: 8A00
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model MES23.5 cells Normal Mus musculus CVCL_J351
In Vivo Model
Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water.

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Response regulation Ferroptosis firstly occurred in a relatively low concentration of ferric ammonium citrate (FAC)-treated group, and then apoptosis appeared in response to the increased iron doses. This was also confirmed in vivo in parkinson's disease transgenic mice and the underlying mechanism might be associated with the p53 signaling pathway, but not MAPK signaling pathway.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Degenerative arthritis ICD-11: FA05
Responsed Regulator Interleukin-1 beta (IL1B) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hCDs (Chondrocytes)
In Vivo Model
Thirty-two 8 weeks old male C57BL/6 mice were used in this study. Eight mice were randomly allocated to the sham surgery group. After anesthetized by intraperitoneal injection of pentobarbital (35 mg/kg), sham surgery group were subjected to sham surgery. Then, destabilized medial meniscus (DMM) were performed to establish the OA model in twenty-four mice. DMM mice were randomly divided into three groups (N=8 for each group): the DMM group, the DMM+0.1mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group. The DMM+0.1 mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group were intraarticularly injected with 0.1 mg/kg or 1 mg/kg ferrostain-1 respectively. The sham surgery group and DMM group were intraarticularly injected with same volume of vehicle. The injection was repeated twice a week for 8 consecutive weeks.

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Response regulation Both IL-1 and FAC induced ferroptosis related protein expression changes in chondrocytes.In this study, we use Interleukin-1 Beta (IL-1) to simulate inflammation and ferric ammonium citrate (FAC) to simulate the iron overload in vitro. Furthermore, inhibition of ferroptosis, by intraarticular injection of ferrostatin-1, in our case, seems to be a novel and promising option for the prevention of osteoarthritis.
References
Ref 1 SIRT1-autophagy axis inhibits excess iron-induced ferroptosis of foam cells and subsequently increases IL-1 and IL-18. Biochem Biophys Res Commun. 2021 Jul 5;561:33-39. doi: 10.1016/j.bbrc.2021.05.011. Epub 2021 May 15.
Ref 2 Ferroptosis was more initial in cell death caused by iron overload and its underlying mechanism in Parkinson's disease. Free Radic Biol Med. 2020 May 20;152:227-234. doi: 10.1016/j.freeradbiomed.2020.03.015. Epub 2020 Mar 23.
Ref 3 Chondrocyte ferroptosis contribute to the progression of osteoarthritis. J Orthop Translat. 2020 Dec 17;27:33-43. doi: 10.1016/j.jot.2020.09.006. eCollection 2021 Mar.