Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0273)
Name
Gossypol acetic acid
Synonyms
Gossypol acetic acid; 12542-36-8; gossypol-Acetic acid; Gossypol acetate; 866541-93-7; Acetate gossypol; AT101; Gossypol (acetic acid); 5453-04-3; (-)-Gossypol acetic acid; (S)-Gossypol (acetic acid); 1189561-66-7; (R)-Gossypol acetic acid; (R)-(-)-Gossypol acetic acid; (S)-Gossypol acetic acid; Gossypol acetate, (R)-; Gossypol acetic acid, R-; AT-101 (acetic acid); Gossypol acetic acid, (R)-; R-(-)-gossypol acetic acid; Gossypol acetic acid clathrate; GOSSYPOLACETATE; NSC 19048; U9GNI6VT5N; (+/-)-Gossypol acetic acid; MLS000028630; MLS002702979; NSC19048; acetic acid;7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde; SMR000058743; 12542-36-8 (ACETIC ACID); NSC-19048; acetic acid compound with (S)-1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde (1:1); 115038-46-5; (+/-)-Gossypol-acetic acid;BL 193 (acetic acid); UNII-U9GNI6VT5N; Acetate-gossypol; GossypolAcOHSalt; Aceticacidgossypol; Gossypol xAcetate; AT101 acetate; AT 101 acetic acid; Opera_ID_1014; Gossypol acetic acid [MI]; SCHEMBL352576; (R)-Gossypol acetic acid salt; (S)-Gossypol acetic acid salt; CHEMBL1516388; Gossypol acetic acid [WHO-DD]; HMS500I15; DTXSID90921593; NIOHNDKHQHVLKA-UHFFFAOYSA-N; HMS3651H13; BCP09006; BCP24040; CCG-39212; HY-15464A; MFCD00058385; NSC727858; s2303; s2812; AKOS022188380; AT-101 (AT101); CS-3859; NSC-727858; NCGC00178279-01; AC-34098; AS-15487; HY-17510; FT-0686636; FT-0768953; G0543; SW197103-3; A13578; A14795; A16323; F85115; F85296; ()-Gossypol-acetic acid;BL 193 (acetic acid); ( inverted exclamation markA)-Gossypol-acetic acid; A900030; A920161; J-005228; 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde acetate salt; 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene-8,8'-dicarbaldehyde - acetic acid (1:1); 732279-26-4; Acetic acid compound with 1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde (1:1); acetic acid compound with 1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthyl-8,8'-dicarbaldehyde (1:1); Acetic acid--1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-di(propan-2-yl)[2,2'-binaphthalene]-8,8'-dicarbaldehyde (1/1); aceticacid;7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde; AT 101 acetic acid; AT101 acetic acid;AT-101 acetic acid; (-)-Gossypol acetic acid; (R)-Gossypol acetic acid; Gossypol acetic acid

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Status
Investigative
Drug Type
Small molecular drug
Structure
3D MOL
2D MOL
Formula
C32H34O10
IUPAC Name
acetic acid;7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde
Canonical SMILES
CC1=CC2=C(C(=C(C(=C2C(C)C)O)O)C=O)C(=C1C3=C(C4=C(C=C3C)C(=C(C(=C4C=O)O)O)C(C)C)O)O.CC(=O)O
InChI
InChI=1S/C30H30O8.C2H4O2/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36;1-2(3)4/h7-12,33-38H,1-6H3;1H3,(H,3,4)
InChIKey
NIOHNDKHQHVLKA-UHFFFAOYSA-N
PubChem CID
227456
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 Ischemia/reperfusion injury ICD-11: DB98
 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
A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast.

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Response regulation Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death.
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 Ischemia/reperfusion injury ICD-11: DB98
 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
A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast.

    Click to Show/Hide
Response regulation Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death.
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 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 Ischemia/reperfusion injury ICD-11: DB98
 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
A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast.

    Click to Show/Hide
Response regulation Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death.
References
Ref 1 Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism. Biomolecules. 2021 Nov 10;11(11):1667. doi: 10.3390/biom11111667.