Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0127)
Name
Isoliquiritigenin
Synonyms
isoliquiritigenin; 961-29-5; 2',4,4'-Trihydroxychalcone; (E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; 4,2',4'-Trihydroxychalcone; 6'-deoxychalcone; Isoliquiritigen; GU 17; 2',4',4-Trihydroxychalcone; Chalcone, 2',4,4'-trihydroxy-; GU-17; C15H12O4; CCRIS 7676; UNII-B9CTI9GB8F; trihydroxychalcone; B9CTI9GB8F; 42'4'-trihydroxychalcone; 13745-20-5; 2-Propen-1-one, 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-, (2E)-; (2E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; CHEBI:310312; trans-2',4,4'-trihydroxychalcone; 1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one; 1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; 2-Propen-1-one, 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-, (E)-; Acrylophenone, 2',4'-dihydroxy-3-(p-hydroxyphenyl)-; CHEMBL129795; GU17; (E)-1-(2,4-Dihydroxy-phenyl)-3-(4-hydroxy-phenyl)-propenone; (2E)-1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one; (E)-1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one; 2-PROPEN-1-ONE, 1-(2,4-DIHYDROXYPHENYL)-3-(4-HYDROXYPHENYL)-; (E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propene-1-one; 1060-19-1; ILG; SMR000112969; GU17;ISL;Isoliquiritigen; SR-01000075499; EINECS 237-316-5; BRN 1914295; iso-Liquiritigenin; MFCD00075907; ILTG; ISLQ; Isoliquiritigenin, powder; Spectrum5_000612; Lopac0_000681; BSPBio_003411; 1-08-00-00707 (Beilstein Handbook Reference); MLS000438943; MLS002207240; MLS006010045; BIDD:ER0235; SCHEMBL161168; SPECTRUM1504200; cid_638278; MEGxp0_001326; 2',4,4'-Trihydroxy-Chalcone; DTXSID2022466; 2'',4'',4-trihydroxychalcone; 2'',4,4''-trihydroxychalcone; ACon1_000047; CHEBI:94010; TRIHYDROXYCHALCONE [INCI]; BCPP000201; HMS2233H18; HMS3262I03; 2,4''-dihydroxy-4-hydroxychalcone; BCP02312; HY-N0102; Tox21_500681; BDBM50042944; CCG-40334; CMLD3_000056; HB4213; LMPK12120096; s2404; Isoliquiritigenin, analytical standard; AKOS001590146; BCP9000795; CS-1745; DB03285; KS-5256; LP00681; SDCCGMLS-0066751.P001; SDCCGSBI-0050660.P004; NCGC00090504-01; NCGC00090504-02; NCGC00090504-03; NCGC00090504-04; NCGC00090504-05; NCGC00090504-06; NCGC00090504-07; NCGC00090504-08; NCGC00090504-24; NCGC00261366-01; AC-33981; EU-0100681; I0822; SW219658-1; C08650; I 3766; I11575; A845551; 2',4'-Dihydroxy-3-(p-hydroxyphenyl)-Acrylophenone; Q-100904; Q3155537; SR-01000075499-1; SR-01000075499-5; BRD-K33583600-001-03-9; BRD-K33583600-001-04-7; 1-(2,4-Dihydroxy-phenyl)-3-(4-hydroxy-phenyl)-propenone; 1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)-prop-2-en-1-one; (E)-1-[2,4-bis(oxidanyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one; InChI=1/C15H12O4/c16-11-4-1-10(2-5-11)3-8-14(18)13-7-6-12(17)9-15(13)19/h1-9,16-17,19H/b8-3

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C15H12O4
IUPAC Name
(E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one
Canonical SMILES
C1=CC(=CC=C1C=CC(=O)C2=C(C=C(C=C2)O)O)O
InChI
InChI=1S/C15H12O4/c16-11-4-1-10(2-5-11)3-8-14(18)13-7-6-12(17)9-15(13)19/h1-9,16-17,19H/b8-3+
InChIKey
DXDRHHKMWQZJHT-FPYGCLRLSA-N
PubChem CID
638278
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 Acute kidney failure ICD-11: GB60
 Disease Info 
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently.

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Response regulation Isoliquiritigenin (ISL) attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation.
Nuclear receptor coactivator 4 (NCOA4)
 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 Driver
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently.

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Response regulation Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation.
References
Ref 1 Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. Ren Fail. 2021 Dec;43(1):1551-1560. doi: 10.1080/0886022X.2021.2003208.