Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0203)
Name |
Ferric ammonium citrate
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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 |
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3D MOL
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Formula |
C6H8FeNO7
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IUPAC Name |
azane;2-hydroxypropane-1,2,3-tricarboxylate;iron(3+)
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Canonical SMILES |
C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.N.[Fe+3]
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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
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InChIKey |
FRHBOQMZUOWXQL-UHFFFAOYSA-K
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PubChem CID |
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