Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0066)
Name
Paraquat
Synonyms
PARAQUAT; 4685-14-7; Paraquat ion; Paraquat dication; 1,1'-Dimethyl-4,4'-bipyridinium; Dimethyl viologen; 4,4'-Bipyridinium, 1,1'-dimethyl-; Methyl viologen (2+); Starfire; Weedol; Spraytop-graze; Dextrone X; Gramoxone; Methyl viologen ion(2+); N,N'-Dimethyl-4,4'-bipyridinium; 1,1'-Dimethyl-4,4'-bipyridyldiylium; CCRIS 7731; 1-methyl-4-(1-methylpyridin-1-ium-4-yl)pyridin-1-ium; HSDB 1668; PRIGLONE; 1,1'-Dimethyl-4,4'-bipyridinium salt; 1,1'-Dimethyl-4,4'-bipyridinium cation; Gramoxone S; PARAQUAT CATION; CHEBI:34905; N,N'-Dimethyl-4,4'-bipyridinium dication; PLG39H7695; DTXSID3034799; 1,1'-dimethyl-4,4'-bipyridium; 1,1'-dimethyl-4,4'-bipyridin-1-ium; PARAQUAT (MART.); PARAQUAT [MART.]; BIPYRIDINIUM, 1,1'-DIMETHYL-4,4'-; MLS001332595; Viologen, Methyl; Paraquat [ANSI:BSI:ISO]; 1,1'-dimethyl-(4,4'-bipyridin)-1,1'-diium; 1,1'-dimethyl-[4,4'-bipyridin]-1,1'-diium; SMR000875209; EINECS 225-141-7; N,N'-Dimethyl-gamma,gamma'-dipyridylium; UNII-PLG39H7695; KHJ; PARAQUAT [HSDB]; PARAQUAT [ISO]; PARAQUAT [MI]; 3240-78-6; ChemDiv3_000231; NCIMech_000502; NCIOpen2_005422; SCHEMBL21652; MLS001304933; BIDD:ER0480; CHEMBL74469; 1,1'-Dimethyl-4,4'-bipyridyldiylium ion (8CI)(9CI); DTXCID1014799; BDBM96275; cid_5351279; 1,1'-Dimethyl,4,4'-bipyridyl; INFDPOAKFNIJBF-UHFFFAOYSA-N; HMS1473K11; 1,1 '-dimethyl-4,4'-bipyridinium; CCG-35984; STK387391; AKOS001483177; IDI1_019549; 1,1'-DIMETHYL-4,4'-BIPYRIDYL; NCGC00166161-02; NCI60_002105; SMR000752910; 1,1'-Dimethyl-4,4'-bipyridyldiylium ion; FT-0606133; FT-0652363; 1,1'-Dimethyl-4,4'-bipyridium bromide (1:2); AC-907/25005209; W-106083; Q26841324; 1,1'-DIMETHYL-[4,4'-BIPYRIDINE]-1,1'-DIIUM; 1-methyl-4-(1-methyl-4-pyridin-1-iumyl)pyridin-1-ium;chloride; 1-methyl-4-(1-methylpyridin-1-ium-4-yl)pyridin-1-ium;chloride

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C12H14N2+2
IUPAC Name
1-methyl-4-(1-methylpyridin-1-ium-4-yl)pyridin-1-ium
Canonical SMILES
C[N+]1=CC=C(C=C1)C2=CC=[N+](C=C2)C
InChI
InChI=1S/C12H14N2/c1-13-7-3-11(4-8-13)12-5-9-14(2)10-6-12/h3-10H,1-2H3/q+2
InChIKey
INFDPOAKFNIJBF-UHFFFAOYSA-N
PubChem CID
15939
TTD Drug ID
D00CAF
Full List of Ferroptosis Target Related to This Drug
Prostaglandin G/H synthase 2 (PTGS2)
 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
Responsed Disease Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

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Response regulation Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)
 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 Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

    Click to Show/Hide
Response regulation Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.
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 Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

    Click to Show/Hide
Response regulation Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.
Cystine/glutamate transporter (SLC7A11)
 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 Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

    Click to Show/Hide
Response regulation Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.
References
Ref 1 Ferritinophagy-Mediated Ferroptosis Involved in Paraquat-Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in PD. Oxid Med Cell Longev. 2021 Jul 26;2021:9961628. doi: 10.1155/2021/9961628. eCollection 2021.