Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0184)
Name
Dexmedetomidine
Synonyms
DEXMEDETOMIDINE; 113775-47-6; Dexmedetomidinum; MPV 1440; Precedex; 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole; 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole; MPV-1440; Dexmedetomidina; (+)-4-((S)-alpha,2,3-Trimethylbenzyl)imidazole; Medetomidine, (s)-; (S)-5-(1-(2,3-Dimethylphenyl)ethyl)-1H-imidazole; Precedex (TN); CHEMBL778; 67VB76HONO; CHEBI:4466; 113775-47-6 (free base); 1H-Imidazole, 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-; 4-[(1~{S})-1-(2,3-dimethylphenyl)ethyl]-1~{H}-imidazole; (S)-4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole; UNII-67VB76HONO; Dexmedetomidine (USAN/INN); Dexmedetomidinum [INN-Latin]; Dexmedetomidina [INN-Spanish]; MFCD00880557; Dexmedetomidine [USAN:INN:BAN]; Dexdor (TN); Tocris-2023; NCGC00025347-01; (S)-4-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole; DEXMEDETOMIDINE [MI]; SCHEMBL26433; DEXMEDETOMIDINE [INN]; GTPL521; DEXMEDETOMIDINE [USAN]; DEXMEDETOMIDINE [VANDF]; (+)-(S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H -imidazole monohydrochloride; DEXMEDETOMIDINE [WHO-DD]; DexmedetomidineHclC13H16N2.Hcl; DTXSID10873388; TPU 006; CUHVIMMYOGQXCV-NSHDSACASA-N; HMS3885M07; DEXMEDETOMIDINE [GREEN BOOK]; BDBM50085683; s3075; AKOS025149503; AKOS026750524; CCG-266586; DB00633; Igalmi (dexmedetomidine sublingual film); NCGC00371080-02; NCGC00371080-09; AS-68685; HY-12719; CS-0012295; SW219607-1; C07450; D00514; EN300-127736; AB01566872_01; AB01566872_02; Q412133; 4-[(1S)-1-(2,3-Dimethylphenyl)ethyl]-1H-imidazol; 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-3H-imidazole; 1H-Imidazole, 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-; 4-[(s)-1-(2,3-dimethyl-phenyl)-ethyl]-1h-imidazole; (+)-4-((S)-.ALPHA.,2,3-TRIMETHYLBENZYL)IMIDAZOLE

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C13H16N2
IUPAC Name
5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole
Canonical SMILES
CC1=C(C(=CC=C1)C(C)C2=CN=CN2)C
InChI
InChI=1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)/t11-/m0/s1
InChIKey
CUHVIMMYOGQXCV-NSHDSACASA-N
PubChem CID
5311068
TTD Drug ID
D0U3DU
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator Transcription factor E2F7 (E2F7) Suppressor
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model SNU-1 cells Gastric adenocarcinoma Homo sapiens CVCL_0099
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 cells Normal Homo sapiens CVCL_EQ22
In Vivo Model
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.

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Response regulation The current work studied the role of Dexmedetomidine (DEX) in gastric cancer cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator Circ_0008035 (circRNA) Suppressor
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model SNU-1 cells Gastric adenocarcinoma Homo sapiens CVCL_0099
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 cells Normal Homo sapiens CVCL_EQ22
In Vivo Model
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.

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Response regulation The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator hsa-mir-302a (Precursor RNA) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model SNU-1 cells Gastric adenocarcinoma Homo sapiens CVCL_0099
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 cells Normal Homo sapiens CVCL_EQ22
In Vivo Model
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.

    Click to Show/Hide
Response regulation The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC.
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 [2]
Target for Ferroptosis Suppressor
Responsed Disease Sepsis ICD-11: 1G40
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mVTs (Mouse ventricular tissues)
In Vivo Model
A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage.

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Response regulation The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury.
Heme oxygenase 1 (HMOX1)
 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/Suppressor
Responsed Disease Sepsis ICD-11: 1G40
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mVTs (Mouse ventricular tissues)
In Vivo Model
A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage.

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Response regulation The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury.
References
Ref 1 Dexmedetomidine promotes ferroptotic cell death in gastric cancer via hsa_circ_0008035/miR-302a/E2F7 axis. Kaohsiung J Med Sci. 2023 Apr;39(4):390-403. doi: 10.1002/kjm2.12650. Epub 2023 Jan 31.
Ref 2 Dexmedetomidine alleviated sepsisinduced myocardial ferroptosis and septic heart injury. Mol Med Rep. 2020 Jul;22(1):175-184. doi: 10.3892/mmr.2020.11114. Epub 2020 May 4.