Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0232)
Name
Seratrodast
Synonyms
SERATRODAST; 112665-43-7; Bronica; 7-phenyl-7-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)heptanoic acid; Abbott 73001; ABT-001; AA-2414; Abbott-73001; AA 2414; (+-)-7-(3,5,6-Trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid; 103185-78-0; A-73001; NSC-759640; DTXSID4021397; 4U58JM421N; MFCD00875701; NCGC00181296-01; Seratrodast [USAN:INN]; DTXCID201397; ABT 001; Bronica (TN); CCRIS 8939; CAS-112665-43-7; A 73001; UNII-4U58JM421N; Seratrodast (JAN/USAN/INN); (+/-)-2,4,5-Trimethyl-3,6-dioxo-zeta-phenyl-1,4-cyclohexadiene-1-heptanoic acid; 7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid; Seratrodast- Bio-X; SERATRODAST [MI]; SERATRODAST [INN]; SERATRODAST [JAN]; SERATRODAST [USAN]; 7-phenyl-7-(2,4,5-trimethyl-3,6-dioxo-cyclohexa-1,4-dien-1-yl)heptanoic acid; (+-)-2,4,5-Trimethyl-3,6-dioxo-zeta-phenyl-1,4-cyclohexadiene-1-heptanoic acid; Benzeneheptanoic acid, zeta-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadien-1-yl)-, (+-)-; SERATRODAST [MART.]; SCHEMBL98402; SERATRODAST [WHO-DD]; MLS006012011; CHEBI:32126; Seratrodast, >=98% (HPLC); ZBVKEHDGYSLCCC-UHFFFAOYSA-N; HMS3264K16; HMS3748I13; Pharmakon1600-01502336; BCP08860; HY-B0774; Tox21_112774; NSC759640; s2072; STL556121; (+/-)-7-(3,5,6-Trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic Acid; AKOS015911825; Seratrodast(AA-2414, ABT-001); Tox21_112774_1; CCG-207903; DB06739; NSC 759640; 7-phenyl-7-(2,4,5-trimethyl-3,6-dioxo-1-cyclohexa-1,4-dienyl)heptanoic acid; NCGC00181296-02; AS-12945; BS164397; SMR002530529; FT-0631064; D01123; AB01563274_01; A802627; L001973; SR-01000944172; J-002813; Q7452735; SR-01000944172-1; 6-(6-Carboxy-1-phenylhexyl)-2,3,5-trimethylbenzoquinone; 7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenylheptanoic acid; 7-phenyl-7-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)heptanoic acid; (+/-)-2,4,5-TRIMETHYL-3,6-DIOXO-.ZETA.-PHENYL-1,4-CYCLOHEXADIENE-1-HEPTANOIC ACID; 7-phenyl-7-[2,4,5-trimethyl-3,6-bis(oxidanylidene)cyclohexa-1,4-dien-1-yl]heptanoic acid; Benzeneoctanoic acid,H-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadien-1-yl)-; 103186-19-2; BENZENEHEPTANOIC ACID, .ZETA.-(2,4,5-TRIMETHYL-3,6-DIOXO-1,4-CYCLOHEXADIEN-1-YL)-, (+/-)-

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Status
Discontinued in Phase 3
Drug Type
Small molecular drug
Structure
Formula
C22H26O4
IUPAC Name
7-phenyl-7-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)heptanoic acid
Canonical SMILES
CC1=C(C(=O)C(=C(C1=O)C)C(CCCCCC(=O)O)C2=CC=CC=C2)C
InChI
InChI=1S/C22H26O4/c1-14-15(2)22(26)20(16(3)21(14)25)18(17-10-6-4-7-11-17)12-8-5-9-13-19(23)24/h4,6-7,10-11,18H,5,8-9,12-13H2,1-3H3,(H,23,24)
InChIKey
ZBVKEHDGYSLCCC-UHFFFAOYSA-N
PubChem CID
2449
TTD Drug ID
D04SPK
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 Status epilepticus ICD-11: 8A66
 Disease Info 
Responsed Regulator Mitogen-activated protein kinase 8 (MAPK8) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated.

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Response regulation Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures.
Cystine/glutamate transporter (SLC7A11)
 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 Suppressor
Responsed Disease Status epilepticus ICD-11: 8A66
 Disease Info 
Responsed Regulator Mitogen-activated protein kinase 8 (MAPK8) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated.

    Click to Show/Hide
Response regulation Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Status epilepticus ICD-11: 8A66
 Disease Info 
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated.

    Click to Show/Hide
Response regulation Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Status epilepticus ICD-11: 8A66
 Disease Info 
Responsed Regulator Mitogen-activated protein kinase 8 (MAPK8) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated.

    Click to Show/Hide
Response regulation Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy.
References
Ref 1 Seratrodast, a thromboxane A2 receptor antagonist, inhibits neuronal ferroptosis by promoting GPX4 expression and suppressing JNK phosphorylation. Brain Res. 2022 Nov 15;1795:148073. doi: 10.1016/j.brainres.2022.148073. Epub 2022 Sep 6.