Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0164)
Name
Nobiletin
Synonyms
Nobiletin; 478-01-3; Hexamethoxyflavone; 3',4',5,6,7,8-Hexamethoxyflavone; 5,6,7,8,3',4'-Hexamethoxyflavone; 2-(3,4-Dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one; NSC-76751; CCRIS 9012; UNII-D65ILJ7WLY; D65ILJ7WLY; NSC 76751; CHEBI:7602; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-chromen-4-one; 4H-1-Benzopyran-4-one, 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-; NSC-618903; CHEMBL76447; Nobiletin (Hexamethoxyflavone); DTXSID30197275; NSC76751; Flavone, 5,6,7,8,3',4'-hexamethoxy; NOBILETIN (USP-RS); NOBILETIN [USP-RS]; FLAVONE, 3',4',5,6,7,8-HEXAMETHOXY-; SMR000156231; MFCD03273560; CPD000156231; Nobiletin, >=97%; NOBILETIN [INCI]; Spectrum2_001697; Spectrum3_000921; Spectrum4_001020; KBioGR_001519; MLS000574877; MLS000759462; MLS000877030; MLS001424129; Nobiletin, analytical standard; SCHEMBL244029; SPECTRUM1505268; SPBio_001654; MEGxp0_000930; ACon1_000921; GTPL12446; KBio3_001922; DTXCID40119766; 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-chromen-4-one; HMS2051D09; HMS2234A09; HMS3373C14; HMS3393D09; HMS3651G20; HEXAMETHOXYFLAVONE [WHO-DD]; HY-N0155; 3'4'5,6,7,8-Hexamethoxyflavone; BDBM50338976; CCG-38781; LMPK12111468; NSC618903; STL565829; AKOS015965334; NOBILETIN, 20% (Technical Grade); AC-1023; CS-5518; NC00186; SDCCGMLS-0066776.P001; NCGC00095703-01; NCGC00095703-02; NCGC00095703-06; NCGC00169228-01; 5,6,7,8,3'',4''-hexamethoxyflavone; AS-17452; NCI60_041691; FT-0686667; N0871; S2333; SW197566-2; A827343; SR-01000712262; Q-100511; Q2402963; SR-01000712262-5; BRD-K06753942-001-02-0; 2-(3,4-Dimethoxy-phenyl)-5,6,7,8-tetramethoxy-chromen-4-one; 4,5,6,7,8,9,10,11,12,13-decahydrocyclododeca[d]oxazole; 4H-1-Benzopyran-4-one,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-; 2-(3,4-Dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one, 9CI

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Structure
Formula
C21H22O8
IUPAC Name
2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one
Canonical SMILES
COC1=C(C=C(C=C1)C2=CC(=O)C3=C(O2)C(=C(C(=C3OC)OC)OC)OC)OC
InChI
InChI=1S/C21H22O8/c1-23-13-8-7-11(9-15(13)24-2)14-10-12(22)16-17(25-3)19(26-4)21(28-6)20(27-5)18(16)29-14/h7-10H,1-6H3
InChIKey
MRIAQLRQZPPODS-UHFFFAOYSA-N
PubChem CID
72344
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Responsed Regulator Glycogen synthase kinase-3 beta (GSK3B) Driver
 Regulator Info 
Pathway Response Pathways in cancer hsa05200
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
Response regulation Nobiletin could induce ferroptosis by regulating the GSK3B-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Responsed Regulator Kelch-like ECH-associated protein 1 (KEAP1) Driver
 Regulator Info 
Pathway Response Pathways in cancer hsa05200
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
Response regulation Nobiletin could induce ferroptosis by regulating the GSK3B-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects.
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 [2]
Target for Ferroptosis Driver
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male Sprague-Dawley (SD) rats (4 weeks old, 90-110 g) were obtained from the Vital River Biological company. Rats were kept in a specific-pathogen-free (SPF) environment, with access to food and tap water at an ambient temperature of 20-22 . All institutional and national guidelines for the care and use of laboratory animals were followed. The protocols were reviewed and approved by the Institution of Animal Care and Use Committee of Renmin Hospital of Wuhan University (IACUC, license no. 20200303).

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Response regulation Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin has therapeutic potential for alleviating myocardial ischemia-reperfusion injury associated with ACSL4- and NCOA4-related ferroptosis.
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 [2]
Target for Ferroptosis Driver
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male Sprague-Dawley (SD) rats (4 weeks old, 90-110 g) were obtained from the Vital River Biological company. Rats were kept in a specific-pathogen-free (SPF) environment, with access to food and tap water at an ambient temperature of 20-22 . All institutional and national guidelines for the care and use of laboratory animals were followed. The protocols were reviewed and approved by the Institution of Animal Care and Use Committee of Renmin Hospital of Wuhan University (IACUC, license no. 20200303).

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Response regulation Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin has therapeutic potential for alleviating myocardial ischemia-reperfusion injury associated with ACSL4- and NCOA4-related ferroptosis.
References
Ref 1 Nobiletin Induces Ferroptosis in Human Skin Melanoma Cells Through the GSK3-Mediated Keap1/Nrf2/HO-1 Signalling Pathway. Front Genet. 2022 Mar 8;13:865073. doi: 10.3389/fgene.2022.865073. eCollection 2022.
Ref 2 Nobiletin alleviates myocardial ischemia-reperfusion injury via ferroptosis in rats with type-2 diabetes mellitus. Biomed Pharmacother. 2023 Jul;163:114795. doi: 10.1016/j.biopha.2023.114795. Epub 2023 May 3.