Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0250)
Name
Bicyclol
Synonyms
bicyclol; 118159-48-1; Methyl 5'-(hydroxymethyl)-7,7'-dimethoxy-[4,4'-bibenzo[d][1,3]dioxole]-5-carboxylate; Bicyclol [WHO-DD]; SY801; 9734122TH2; 4,4'-Bi-1,3-benzodioxole)-5-carboxylic acid, 5'-(hydroxymethyl)-7,7'-dimethoxy-, methyl ester; 5'-(hydroxymethyl)-7,7'-dimethoxy-[4,4'-bi-1,3-benzodioxole]-5-carboxylic acid, methyl ester; UNII-9734122TH2; SY 801; methyl 4-[5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate; CHEMBL482035; SCHEMBL9600725; Bicyclol, >=98% (HPLC); DTXSID30152026; BCP25554; HY-B0766; s6453; 6-methoxycarbonyl-6'-hydroxymethyl-2,3,2',3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl; NCGC00408803-01; 4,4'-bi-(1,3-benzodioxole)-5-carboxylic acid, 5'-(hydroxymethyl)-7,7'-dimethoxy-, methyl ester; AS-16866; F85022; J-003718; Q27271958

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Structure
Formula
C19H18O9
IUPAC Name
methyl 4-[5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate
Canonical SMILES
COC1=C2C(=C(C(=C1)CO)C3=C4C(=C(C=C3C(=O)OC)OC)OCO4)OCO2
InChI
InChI=1S/C19H18O9/c1-22-11-4-9(6-20)13(17-15(11)25-7-27-17)14-10(19(21)24-3)5-12(23-2)16-18(14)28-8-26-16/h4-5,20H,6-8H2,1-3H3
InChIKey
KXMTXZACPVCDMH-UHFFFAOYSA-N
PubChem CID
9821754
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
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 Injury of intra-abdominal organs ICD-11: NB91
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
The mice were treated with intraperitoneal administration (i.p.) of oil (control group) or a mixture of CCl4 (50%) and oil (50%) at a dosage of 2 ml/kg body weight. In the bicyclol-treated group, mice accepted administration of 200 mg/kg (using 0.5% carboxymethyl cellulose as solvent) by gavage three times a day 1 h before CCl4 exposure, while other groups accepted vehicles of the equal volume. Fer-1 was prepared in DMSO (5 mg/kg), andi.p. injected into mice once 1 h before CCl4 exposure. The dosage of bicyclol was consistent with our previous work. The mice were then sacrificed to collect liver and serum samples after 24 or 48 h.

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Response regulation Bicyclol exerted its hepatoprotection by preventing the aforesaid ferroptotic process. Furthermore, bicyclol alleviated erastin-induced cellular inviability, destruction, and lipid peroxidation in vitro. Knockdown of GPX4 diminished these protective activities against perturbations associated with ferroptosis in L-O2 hepatocytes. Additionally, Nrf2 silencing drastically reduced GPX4 levels, and further impeded the medicinal effects of bicyclol. In summary, positively regulating Nrf2-GPX4 axis by bicyclol can prevent ferroptosis in CCl4-induced acute liver injury in mice.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Injury of intra-abdominal organs ICD-11: NB91
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
The mice were treated with intraperitoneal administration (i.p.) of oil (control group) or a mixture of CCl4 (50%) and oil (50%) at a dosage of 2 ml/kg body weight. In the bicyclol-treated group, mice accepted administration of 200 mg/kg (using 0.5% carboxymethyl cellulose as solvent) by gavage three times a day 1 h before CCl4 exposure, while other groups accepted vehicles of the equal volume. Fer-1 was prepared in DMSO (5 mg/kg), andi.p. injected into mice once 1 h before CCl4 exposure. The dosage of bicyclol was consistent with our previous work. The mice were then sacrificed to collect liver and serum samples after 24 or 48 h.

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Response regulation Bicyclol exerted its hepatoprotection by preventing the aforesaid ferroptotic process. Furthermore, bicyclol alleviated erastin-induced cellular inviability, destruction, and lipid peroxidation in vitro. Knockdown of GPX4 diminished these protective activities against perturbations associated with ferroptosis in L-O2 hepatocytes. Additionally, Nrf2 silencing drastically reduced GPX4 levels, and further impeded the medicinal effects of bicyclol. In summary, positively regulating Nrf2-GPX4 axis by bicyclol can prevent ferroptosis in CCl4-induced acute liver injury in mice.
References
Ref 1 Regulating Nrf2-GPx4 axis by bicyclol can prevent ferroptosis in carbon tetrachloride-induced acute liver injury in mice. Cell Death Discov. 2022 Sep 7;8(1):380. doi: 10.1038/s41420-022-01173-4.