Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0376)
| Name |
Furosine dihydrochloride
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| Synonyms |
furosine; 19746-33-9; (2S)-2-amino-6-[[2-(furan-2-yl)-2-oxoethyl]amino]hexanoic acid; Epsilon-N-(2-furoyl-methyl)-L-lysine 2hcl; Furosine 2HCl; N6-[2-(2-furanyl)-2-oxoethyl]-L-Lysine; N6-(2-(2-Furanyl-2-oxoethyl))-L-lysine; C9XU89FM3X; Nepsilon-(2-Furoylmethyl)-L-lysine; Epsilon-N-(2-furoyl-methyl)-L-lysine; Epsilon-n-(2-furoyl-methyl)-l-lysine2hcl; W-201729; (2S)-2-AZANYL-6-((2-(FURAN-2-YL)-2-OXIDANYLIDENE-ETHYL)AMINO)HEXANOIC ACID
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| Structure |
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| Formula |
C12H18N2O4
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| IUPAC Name |
(2S)-2-amino-6-[[2-(furan-2-yl)-2-oxoethyl]amino]hexanoic acid
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| Canonical SMILES |
C1=COC(=C1)C(=O)CNCCCCC(C(=O)O)N
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| InChI |
InChI=1S/C12H18N2O4/c13-9(12(16)17)4-1-2-6-14-8-10(15)11-5-3-7-18-11/h3,5,7,9,14H,1-2,4,6,8,13H2,(H,16,17)/t9-/m0/s1
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| InChIKey |
YQHPCDPFXQXCMV-VIFPVBQESA-N
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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 | Kidney injury | ICD-11: NB92 | |||
| Responsed Regulator | Androgen receptor (AR) | Driver | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Cell Process | Cell ferroptosis | ||||
| In Vitro Model | mPKCs (Mouse primary kidney cells) | ||||
| In Vivo Model |
A total of 60 ICR female mice (20 ± 2g, 5 mice/group) were divided into 12 groups (control and 10 furosine treatment groups). Furosine was dissolved in distilled water and a dose of 0.24 g/kg b.w. was administered by gavage or tail vein injection (0.2 mL volume per mouse) once at the beginning. This dose was chosen based on the median lethal dose (LD50) determined in previous acute toxicity experiments, in which the LD50 of furosine was 1.6 g/kg b.w. Mice were fasted for 4 h prior to dosing; animals were sacrificed at 0 (controls), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after administration, and kidney tissue was dissected and blood samples were collected.
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| Response regulation | Furosine might decrease the activity of GPX4 via AR, thereby disrupting the conversion of peroxides into non-toxic reduced forms. Once GPX4 loses its reduction activity, excessivelipid peroxidationin kidney cells can lead to cell death by ferroptosis. To conclude, the study demonstrated for the first time the toxicity of furosine toward kidney injury. | ||||