Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0015)
Name
Rotenone
Synonyms
rotenone; 83-79-4; Dactinol; Paraderil; Barbasco; Tubatoxin; (-)-Rotenone; (-)-cis-Rotenone; Rotocide; Derrin; Derris; Rotenon; Nicouline; Ronone; Canex; Deril; Liquid Derris; Cube-Pulver; Dri-Kil; Rotessenol; Noxfire; Rotefive; Rotefour; Rotenox; Cubor; Haiari; Mexide; Chem-Mite; Cenol garden dust; Curex flea duster; Tubotoxin; Gerane; Prentox; Ro-Ko; Synpren; Derris (insecticide); Pb-nox; Rotenox 5EC; 5'-beta-Rotenone; Green Cross Warble Powder; Caswell No. 725; Extrax; Rotenone, dehydro; Foliafume E.C.; ENT 133; Rotenone, commercial; CCRIS 895; HSDB 1762; NCI-C55210; 5'beta-Rotenone; EPA Pesticide Chemical Code 071003; AI3-00133; C23H22O6; NSC26258; Rotenona; Derris resins; MLS000738056; CHEMBL429023; 1,2,12,12a-Tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-(1)benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one; DTXSID6021248; CHEBI:28201; 03L9OT429T; Rotacide E.C.; CUBE; NSC-26258; (1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-alpha-isopropenyl-8,9-dimethoxy-; (12aS,6aS,2R)-8,9-dimethoxy-2-(1-methylvinyl)-1,2-dihydrochromano[3,4-b]furano [2,3-h]chroman-6-one; (2R,6aS,12aS)-8,9-dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one; (2R-(2alpha,6aalpha,12aalpha))-1,2,12,12a-Tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)(1)benzopyrano(3,4-b)furo(2,3-h)benzopyran-6(6aH)-one; 1,2,12,12aalpha-Tetrahydro-2a-isopropenyl-8,9-dimethoxy(1)benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one; NCGC00017358-05; Nekoe; (1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, (2R-(2alpha,6aalpha,12aalpha))-; (1S,6R,13S)-16,17-dimethoxy-6-prop-1-en-2-yl-2,7,20-trioxapentacyclo[11.8.0.03,11.04,8.014,19]henicosa-3(11),4(8),9,14,16,18-hexaen-12-one; (2R,6aS,12aS)-1,2,12,12a-Tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-[1]benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one; (2R,6aS,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxychromeno(3,4-b)furo(2,3-h)chromen-6-one; [2R-(2alpha,6aalpha,12aalpha)]-1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)[1]benzopyrano[3,4-b]furo[2,3-H][1]benzopyran-6(6aH)-one; Rotenona [Spanish]; DTXCID901248; Rotenone [BSI:ISO]; Protax; 5'.beta.-Rotenone; CAS-83-79-4; (1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, (2R,6aS,12aS)-; (2R,6aS,12aS)-1,2,6,6a,12,12a- hexahydro-2-isopropenyl-8,9- dimethoxychromeno[3,4-b] furo(2,3-h)chromen-6-one; (2R,6aS,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furo[2,3-h]chromen-6-one; (2R,6aS,12aS)-2-isopropenyl-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one; (2R,6aS,12aS)-8,9-Dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydrofuro[2',3':7,8][1]benzopyrano[2,3-c][1]benzopyran-6(6aH)-one; [1]Benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, (2R,6aS,12aS)-; SR-01000076110; EINECS 201-501-9; NSC 26258; Rotenoid; Roteonone; UNII-03L9OT429T; WLN: T G5 D6 B666 CV HO MO POT&TT&J IY1&U1 SO1 TO1; 5''beta-rotenone; 5'b-Rotenone; Rotocide E.C.; (1)Benzopyrano[3,3-h](1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-.alpha.-iospropenyl-8,9-dimethoxy-; [1]Benzopyrano[3,3-h][1]benzopyran-6(6a.alpha.H)-one, 1,2,12,12a.alpha.-tetrahydro-2.alpha.-isopropenyl-8,9-dimethoxy-; [1]Benzopyrano[3,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, [2R-(2.alpha.,6a.alpha.,12a.alpha.)]-; [1]Benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, [2R-(2alpha,6aalpha,12aalpha)]-; Derris, JMAF; Prestwick_542; Rotenone (7CI); Rotenone, >=95%; Spectrum_000065; ROTENONE [HSDB]; ROTENONE [ISO]; ROTENONE [MI]; Spectrum2_000457; Spectrum3_000158; Spectrum4_001638; Spectrum5_000455; ROTENONE [MART.]; Lopac0_001112; SCHEMBL42253; BSPBio_001896; isopropenyl(dimethoxy)[?]one; KBioGR_002075; KBioSS_000465; SPECTRUM200013; (2R-(6aalpha,12aalpha)-1,2-Dihydro-2-isopropenyl-8,9-dimethoxychromano(3,4-b)furo(2,3-h)chroman-6-on; DivK1c_000947; ROTENONE [GREEN BOOK]; SPBio_000534; HMS502P09; KBio1_000947; KBio2_000465; KBio2_003033; KBio2_005601; KBio3_001116; inhibits NADH2 oxidation to NAD; NSC8505; JUVIOZPCNVVQFO-HBGVWJBISA-N; NINDS_000947; HMS3263O06; BCP07278; HY-B1756; NSC-8505; TNP00301; Tox21_110819; Tox21_201904; Tox21_300695; Tox21_501112; BDBM50135527; CCG-39886; HB5398; LMPK12060007; AKOS004910398; Tox21_110819_1; CS-6067; DB11457; LP01112; SDCCGMLS-0066415.P001; SDCCGSBI-0051081.P003; IDI1_000947; Rotenone 100 microg/mL in Acetonitrile; NCGC00017358-01; NCGC00017358-02; NCGC00017358-03; NCGC00017358-04; NCGC00017358-06; NCGC00017358-07; NCGC00017358-08; NCGC00017358-09; NCGC00017358-10; NCGC00017358-11; NCGC00017358-14; NCGC00017358-15; NCGC00017358-22; NCGC00094382-01; NCGC00094382-02; NCGC00094382-03; NCGC00094382-04; NCGC00094382-05; NCGC00254603-01; NCGC00259453-01; NCGC00261797-01; AC-31290; AS-10183; NCI60_002093; SMR000393729; EU-0101112; R0090; Rotenone, PESTANAL(R), analytical standard; C07593; R 8875; Q412388; SR-01000076110-2; SR-01000076110-5; SR-01000076110-6; W-104134; BRD-K08316444-001-01-9; BRD-K08316444-001-05-0; (2R,6AS,12AS)-1,2,12,12A-TETRAHYDRO-8,9-DIMETHOXY-2-(1-METHYLETHENYL)(1)BENZOPYRANO(3,4-B)FURO(2,3-H)(1)BENZOPYRAN-6(6AH)-ONE; (2R-(6aalpha,12aalpha)-1,2-Dihydro-2-isopropenyl-8,9-dimethoxychromano(3,4-b)furo(2,3-h)chroman-6-one; [1]Benzopyrano[3,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-.alpha.-isopropenyl-8,9-dimethoxy-; [1]Benzopyrano[3,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-isopropenyl-8,9-dimethoxy-; [1]Benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aalphaH)-one, 1,2,12,12aalpha-tetrahydro-2alpha-isopropenyl-8,9-dimethoxy- (8CI); [1]Benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, (2R,6aS,12aS)- (9CI); 1,2,12,12a-Tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-[1]benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one, 9CI; Tubatoxin 1,2,12,12a,-Tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-[1]benzopyrano[3,4-b]furo[2,3-h][1]-benzopyran-6(6aH)-one

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C23H22O6
IUPAC Name
(1S,6R,13S)-16,17-dimethoxy-6-prop-1-en-2-yl-2,7,20-trioxapentacyclo[11.8.0.03,11.04,8.014,19]henicosa-3(11),4(8),9,14,16,18-hexaen-12-one
Canonical SMILES
CC(=C)C1CC2=C(O1)C=CC3=C2OC4COC5=CC(=C(C=C5C4C3=O)OC)OC
InChI
InChI=1S/C23H22O6/c1-11(2)16-8-14-15(28-16)6-5-12-22(24)21-13-7-18(25-3)19(26-4)9-17(13)27-10-20(21)29-23(12)14/h5-7,9,16,20-21H,1,8,10H2,2-4H3/t16-,20-,21+/m1/s1
InChIKey
JUVIOZPCNVVQFO-HBGVWJBISA-N
PubChem CID
6758
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Intracerebral hemorrhage ICD-11: 8B00
 Disease Info 
Responsed Regulator 60S ribosomal protein L8 (RPL8) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Six-to-eight week old male ICR mice were purchased from the Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China). All animal procedures have been approved by the Institutional Animal Care and Use Committee of Ruijin hospital, Shanghai Jiao Tong University (Shanghai, China). Efforts were made as much as possible to reduce the number of mice used and to minimize suffering. Herein, a total of 51 mice were randomly divided into 3 groups: (i) sham group (n = 15), (ii) ICH group (n = 18), and (iii) ICH + Rot group (n = 18). To be specific, the current study was divided into two parts of the experimental design. Part 1: to observe the effects of Rot on the mitochondria-related genes, iron levels, MDA levels, SOD activity, hematoma volume, brain edema, and ultrastructural changes of mitochondria, animals were randomly divided into the sham group (n = 9), ICH group (n = 12), and ICH + Rot group (n = 12). All mice were euthanized at 3 d after operation and brain samples were harvested, as per our previously described reports. Part 2: to observe the effect of Rot on neurological deficits following ICH, 18 mice were randomly divided into additional 3 groups (sham group, ICH group, and ICH + Rot group). We evaluated mNSS scores at 1, 3, 7, and 14 days after ICH. We also assessed the memory function with the MWM test at 14 days after ICH.

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Response regulation Intracerebral hemorrhage induced significant mitochondrial dysfunction and that mitochondrial inhibitor rotenone can trigger and enhance neuronal ferroptosis. The ferroptosis protein markers ACSL4, COX-2, xCT, RPL8, and GPX4 were significantly upregulated in the hemin group. Rot treatment further enhanced hemin-induced upregulation of ACSL4, COX-2, xCT, RPL8, and GPX4 levels.
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 Intracerebral hemorrhage ICD-11: 8B00
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model rPCNs (Rat primary cortical neurons)
In Vivo Model
Six-to-eight week old male ICR mice were purchased from the Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China). Herein, a total of 51 mice were randomly divided into 3 groups: (i) sham group (n = 15), (ii) ICH group (n = 18), and (iii) ICH + Rot group (n = 18). All mice were euthanized at 3 d after operation and brain samples were harvested, as per our previously described reports.

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Response regulation Single rotenone administration markedly inhibited neuronal viability, promoted iron accumulation, increased malondialdehyde (MDA) contents, decreased total superoxide dismutase (SOD) activity, and downregulated ferroptosis-related proteins RPL8, COX-2, xCT, ASCL4, and GPX4 in primary neurons. Together, our data revealed that intracerebral hemorrhage induced significant mitochondrial dysfunction and that mitochondrial inhibitor rotenone can trigger and enhance neuronal ferroptosis.
References
Ref 1 Mitochondrial Inhibitor Rotenone Triggers and Enhances Neuronal Ferroptosis Following Intracerebral Hemorrhage. ACS Chem Neurosci. 2023 Mar 15;14(6):1071-1079. doi: 10.1021/acschemneuro.2c00308. Epub 2023 Feb 27.