Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0008)
Name
Resveratrol
Synonyms
resveratrol; 501-36-0; trans-resveratrol; 3,4',5-Trihydroxystilbene; (E)-5-(4-Hydroxystyryl)benzene-1,3-diol; 3,5,4'-Trihydroxystilbene; (E)-resveratrol; Resvida; 3,4',5-Stilbenetriol; 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol; 3,4',5-Trihydroxy-trans-stilbene; Biofort; Cuspidatin; SRT 501; SRT-501; (E)-5-(p-Hydroxystyryl)resorcinol; Resveratrol p 5; SRT501; Resveratrol(e)-form; 5-[(1E)-2-(4-Hydroxyphenyl)ethenyl]-1,3-benzenediol; 3,5,4'-Trihydroxy-trans-stilbene; Melinjo resveratrol 20; CHEBI:45713; Srt 501m; trans-3,4',5-trihydroxystilbene; 5-[(E)-2-(4-hydroxyphenyl)vinyl]benzene-1,3-diol; 3,4',5-trihydroxy-stilbene; NSC 327430; NSC-327430; trans-1,2-(3,4',5-Trihydroxydiphenyl)ethylene; CCRIS 8952; 5-[2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol; DTXSID4031980; UNII-Q369O8926L; HSDB 7571; 5-((1E)-2-(4-Hydroxyphenyl)ethenyl)-1,3-benzenediol; Ca 1201; C14H12O3; 1,3-Benzenediol, 5-(2-(4-hydroxyphenyl)ethenyl)-, (E)-; 1,3-Benzenediol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-; BIA 6-512; BIA-6-512; NSC327430; CHEMBL165; Q369O8926L; (E)-5-[2-(4-hydroxyphenyl)ethenyl]-1,3-benzendiol; MLS000069735; DTXCID2011980; CHEBI:27881; trans-3,4',5 - trihydroxystilbene; (E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol; 133294-37-8; SMR000058206; RESVERATROL (MART.); RESVERATROL [MART.]; (E)-5-[2-(4-Hydroxyphenyl)ethenyl]-1,3-benzenediol; 1,3-Benzenediol, 5-((E)-2-(4-hydroxyphenyl)ethenyl)-; Resveratol; TRANS-RESVERATROL (USP-RS); TRANS-RESVERATROL [USP-RS]; 5-((E)-2-(4-HYDROXYPHENYL)-ETHENYL) BENZENE-1,3 DIOL; MFCD00133799; trans Resveratrol; 5-(2-(4-hydroxyphenyl)ethenyl)benzene-1,3-diol; SR-01000000163; 5-((E)-2-(4-hydroxyphenyl)vinyl)benzene-1,3-diol; 1,3-Benzenediol, 5-[(E)-2-(4-hydroxyphenyl)ethenyl]-; 3fts; 4jaz; 4qer; Resveratrol, E-; Resveratrol,(S); KUC104385N; Stilbene, 2f; TaxusChinensisiRehd; NCGC00015894-02; CAS-501-36-0; STL; Prestwick_619; Resveratrol, trans-; KSC-10-164; RM-1812; Opera_ID_586; RESVERATROL [MI]; Prestwick2_000508; Prestwick3_000508; Spectrum5_000552; RESVERATROL [HSDB]; RESVERATROL [INCI]; R 5010; RESVERATROL [VANDF]; 1,3-Benzenediol, 5-[(1Z)-2-(4-hydroxyphenyl)ethenyl]-; Lopac0_001111; REGID_for_CID_6240; SCHEMBL19425; BSPBio_000435; BSPBio_001114; BSPBio_003461; RESVERATROL [WHO-DD]; MLS001055357; MLS001076538; MLS001424228; MLS002207121; MLS002222231; SPECTRUM1502223; CU-01000001503-3; BPBio1_000479; cid_445154; GTPL8741; SGCUT00007; Resveratrol, analytical standard; REGID_for_CID_445154; BDBM23926; Resveratrol, >=99% (HPLC); AMY5760; 2l98; BCPP000091; HMS1362H15; HMS1569F17; HMS1792H15; HMS1921N04; HMS1990H15; HMS2052I09; HMS2096F17; HMS2232A18; HMS3263O04; HMS3403H15; HMS3412O14; HMS3649A20; HMS3676O14; BCP01416; to_000079; Tox21_110257; Tox21_201374; Tox21_303376; Tox21_501111; AC-727; BBL028252; CCG-38874; HB4055; LMPK13090005; s1396; STL146386; AKOS005720936; Tox21_110257_1; CS-1050; DB02709; KS-5047; LP01111; NC00349; SDCCGMLS-0002998.P003; SDCCGSBI-0051080.P003; IDI1_002152; NCGC00017352-05; NCGC00017352-06; NCGC00017352-07; NCGC00017352-08; NCGC00017352-09; NCGC00017352-10; NCGC00017352-11; NCGC00017352-12; NCGC00017352-13; NCGC00017352-14; NCGC00017352-15; NCGC00017352-16; NCGC00017352-17; NCGC00017352-18; NCGC00017352-19; NCGC00017352-24; NCGC00017352-31; NCGC00017352-39; NCGC00024003-00; NCGC00024003-04; NCGC00024003-05; NCGC00024003-06; NCGC00024003-07; NCGC00024003-08; NCGC00024003-09; NCGC00024003-10; NCGC00024003-11; NCGC00024003-12; NCGC00024003-13; NCGC00024003-14; NCGC00257465-01; NCGC00258925-01; NCGC00261796-01; AS-12413; HY-16561; EU-0101111; R0071; Resveratrol, Vetec(TM) reagent grade, 98%; SW196786-4; trans [2,5,4'-trihydroxydiphenyl] ethylene; C03582; N88795; 5-[2-(4-hydroxyphenyl)vinyl]-1,3-benzenediol; AB00052942-29; AB00052942_31; trans-Resveratrol 100 microg/mL in Acetonitrile; A827984; Q407329; 5-[(E)-2-(4-Hydroxyphenyl)vinyl]-1,3-benzoldiol; SR-01000000163-3; SR-01000000163-4; SR-01000000163-9; 5-[(E)-2-(4-Hydroxyphenyl)ethenyl]benzol-1,3-diol; 5-[(E)-2-(4-Hydroxyphenyl)vinyl]-1,3-benzenediol; 5[(E)-2-(4-Hydroxyphenyl)-vinyl]benzene 1,3-diol; BRD-K25591257-001-01-2; BRD-K80738081-001-06-2; BRD-K80738081-001-07-0; BRD-K80738081-001-09-6; BRD-K80738081-001-10-4; BRD-K80738081-001-23-7; SR-01000000163-10; SR-01000000163-11; SR-01000000163-16; (E)-1-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethene; (E)1-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethene; 5-((1E)-2-(4-hydroxyphenyl)ethenyl)benzene-1,3-diol; 5-[(1E)-2-(4-Hydroxyphenyl)ethenyl]-1,3,benzenediol; Resveratrol, certified reference material, TraceCERT(R); Resveratrol, European Pharmacopoeia (EP) Reference Standard; 1,3-Benzenediol, 5-(2-(4-hydroxyphenyl)-ethenyl)-, (E)-; 533C1DA0-4104-42B5-9D32-9265F40857E4; trans-Resveratrol, United States Pharmacopeia (USP) Reference Standard; 3,4',5-Trihydroxy-trans-stilbene 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol; (E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol(E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol; 31100-06-8; InChI=1/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1

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Status
Phase 3
Drug Type
Small molecular drug
Structure
Formula
C14H12O3
IUPAC Name
5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol
Canonical SMILES
C1=CC(=CC=C1C=CC2=CC(=CC(=C2)O)O)O
InChI
InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+
InChIKey
LUKBXSAWLPMMSZ-OWOJBTEDSA-N
PubChem CID
445154
TTD Drug ID
D0U3EP
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Sepsis ICD-11: 1G40
 Disease Info 
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model hCMs (Human cardiomyocytes)
In Vivo Model
Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1.

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Response regulation Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Sepsis ICD-11: 1G40
 Disease Info 
Responsed Regulator mmu-miR-149-3p (miRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model hCMs (Human cardiomyocytes)
In Vivo Model
Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1.

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Response regulation Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Diabetes mellitus ICD-11: 5A10
 Disease Info 
Responsed Regulator Peroxisome proliferator-activated receptor gamma (PPARG) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MIN6 cells Insulinoma Mus musculus CVCL_0431
Response regulation Acrolein is a typical food and environmental pollutant and a risk factor for diabetes. Resveratrol, an antioxidant natural product, may relieve ER stress and upregulate PPAR expression, thereby inhibiting acrolein-induced ferroptosis.
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 [3]
Target for Ferroptosis Suppressor
Responsed Disease Cardiomyopathy ICD-11: BC43
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Adult male C57BL/6J mice weighing 20 ± 2 g were purchased from Chongqing Tengxin Biotechnology. Mice were housed at 22 with a 12 h light/dark cycle with free access to food and water. The cardiotoxicity mice model was induced by intraperitoneal injection of 5-FU (30 mg/kg) for 7 days. The cardiotoxicity mice were randomly divided into five groups: model group (normal saline), Res low, medium, high dose group (1, 2, 4 mg/kg) and Fer-1 positive control group (2.5 mg/kg). These mice were given Res or Fer-1 once a day for 3 weeks, with the body weight being recorded. Then, the mice were euthanized, blood samples and heart tissue were collected.

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Response regulation Resveratrol (Res) attenuated 5-FU-induced bodyweight reduction, restored the cardiac dysfunction and reduced the activity of oxidative stress. Furthermore, inhibition of GPX4-mediated ferroptosis was the protective mechanisms of Res against 5-FU-induced cardiotoxicity.
References
Ref 1 Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice. Am J Physiol Endocrinol Metab. 2022 Jul 1;323(1):E21-E32. doi: 10.1152/ajpendo.00227.2021. Epub 2022 May 9.
Ref 2 Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress- related PERK pathway in MIN6 cells. Toxicology. 2022 Jan 15;465:153048. doi: 10.1016/j.tox.2021.153048. Epub 2021 Nov 20.
Ref 3 Resveratrol alleviated 5-FU-induced cardiotoxicity by attenuating GPX4 dependent ferroptosis. J Nutr Biochem. 2023 Feb;112:109241. doi: 10.1016/j.jnutbio.2022.109241. Epub 2022 Nov 26.