Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0108)
Name
Ketamine
Synonyms
ketamine; dl-Ketamine; Ketaject; Special K; Ketalar; (+-)-Ketamine; CI 581 base; Calypsol; Ketaminum; CLSTA 20; 6740-88-1; (+/-)-Ketamine; narketan; Cetamina; Ketanest; Tekam; Ketalar base; 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone; 2-(Methylamino)-2-(2-chlorophenyl)cyclohexanone; Ursotamin; Vetaket; Ketamine Base; KETAMINE HCL; Anaket v; 2-(o-Chlorophenyl)-2-(methylamino)-cyclohexanone; Special K [street name]; Clorketam 1000; Ketasol 100; Imalgene 1000; ketamina; NSC 70151; EINECS 229-804-1; NSC-70151; Ketamine (INN); UNII-690G0D6V8H; BRN 2216965; CHEBI:6121; 100477-72-3; DTXSID8023187; cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-; HSDB 2180; 690G0D6V8H; 2-(2-Chloro-phenyl)-2-methylamino-cyclohexanone; CHEMBL742; 2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one; (+/-)-2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone; DTXCID703187; Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-, (+-)-; Cyclohexanone, 2-(o-chlorophenyl)-2-(methylamino)-, (+-)-; KETAFOL COMPONENT KETAMINE; PMI-150; EC 229-804-1; 2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone; Cyclohexanone, 2-(o-chlorophenyl)-2-(methylamino)-; DEA No. 7285; NCGC00159480-02; NCGC00159480-03; Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-, (+/-)-; KETAMINE [INN]; Special K (street name); Ketamine [INN:BAN]; Ketaminum [INN-Latin]; Cetamina [INN-Spanish]; Ketoject; CAS-6740-88-1; Tekam (TN); Ketaminum (Latin); Ketolar (Salt/Mix); Vetalar (Salt/Mix); Kalipsol (Salt/Mix); Ketanest (Salt/Mix); KETAMINE [HSDB]; KETAMINE [MI]; KETAMINE [VANDF]; (.+/-.)-Ketamine; KETAMINE [WHO-DD]; Cyclohexanone, (.+-.)-; SCHEMBL16103; MLS001331674; DivK1c_000217; GTPL4233; (+/-)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone; SCHEMBL17084881; KBio1_000217; N01AX03; NINDS_000217; HMS2272G05; NSC70151; Tox21_111703; Tox21_111704; BDBM50044140; DB01221; IDI1_000217; SMR000238141; C07525; D08098; Q243547; 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone #; J-505587; (.+/-.)-2-(O-Chlorophenyl)-2-(methylamino)cyclohexanone; 2-(2-Chloro-phenyl)-2-methylamino-cyclohexanone(Ketamine); Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)- (9CI); Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-, (+-)- (9CI); Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)-, (.+/-.)-; Cyclohexanone, 2-(o-chlorophenyl)-2-(methylamino)-, (.+/-.)-; Cyclohexanone, 2-(o-chlorophenyl)-2-(methylamino)-, (+/-)- (8CI)

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Structure
Formula
C13H16ClNO
IUPAC Name
2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one
Canonical SMILES
CNC1(CCCCC1=O)C2=CC=CC=C2Cl
InChI
InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3
InChIKey
YQEZLKZALYSWHR-UHFFFAOYSA-N
PubChem CID
3821
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Regulator PVT1 (IncRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
BALB/c nude mice (age 6 weeks) were brought from the Laboratory Animal Center of Chinese Academy of Sciences (China). HepG2 cell suspension (100 uL, 5 x 105 per site) was hypodermically inoculated into the fat pad of mice. Tumor volume was calculated as follows: tumor volume (mm3) = 0.5 x width (mm)2 x length (mm). When tumor size reached 100 mm3, mice were treated with ketamine (20 mg/kg) or saline intraperitoneally. The mice were succumbed to death when tumor size reached 1000 mm3. Tumors were isolated and weighted. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978).

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Response regulation LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of liver cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Regulator hsa-miR-214-3p (miRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
BALB/c nude mice (age 6 weeks) were brought from the Laboratory Animal Center of Chinese Academy of Sciences (China). HepG2 cell suspension (100 uL, 5 x 105 per site) was hypodermically inoculated into the fat pad of mice. Tumor volume was calculated as follows: tumor volume (mm3) = 0.5 x width (mm)2 x length (mm). When tumor size reached 100 mm3, mice were treated with ketamine (20 mg/kg) or saline intraperitoneally. The mice were succumbed to death when tumor size reached 1000 mm3. Tumors were isolated and weighted. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978).

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Response regulation LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of liver cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Histone acetyltransferase KAT5 (KAT5) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
Response regulation The treatment of Ketamine induced the levels of MDA, lipid ROS, and Fe2+, while KAT5 or GPX4 overexpression could reverse this effect in breast cancer cells. Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis. Ketamine may serve as a potential therapeutic strategy for breast cancer.
References
Ref 1 Ketamine Induces Ferroptosis of Liver Cancer Cells by Targeting lncRNA PVT1/miR-214-3p/GPX4. Drug Des Devel Ther. 2021 Sep 18;15:3965-3978. doi: 10.2147/DDDT.S332847. eCollection 2021.
Ref 2 Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis. Biochem Biophys Res Commun. 2021 Dec 31;585:111-116. doi: 10.1016/j.bbrc.2021.11.029. Epub 2021 Nov 12.