General Information of the Drug (ID: ferrodrug0306)
Name
Fatostatin
Synonyms
FATOSTATIN; Fatostatin A; 125256-00-0; 4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole; 2-(2-propylpyridin-4-yl)-4-(p-tolyl)thiazole; CHEMBL1621019; 4-[4-(4-methylphenyl)-1,3-thiazol-2-yl]-2-propylpyridine; MLS000332366; SMR000221636; 2-Propyl-4-(4-p-tolyl-thiazol-2-yl)-pyridine; 4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole;hydrobromide; Fatostatin;125B11; Oprea1_120708; SCHEMBL2742732; BDBM78179; CHEBI:95052; cid_2850562; ZROSUBKIGBSZCG-UHFFFAOYSA-N; AMY41632; BCP20994; s9785; STK326446; AKOS005434229; CS-5810; AC-35652; BS-15072; HY-14452; 2-(2-propyl-4-pyridyl)-4-(p-tolyl)thiazole; D84076; 4-(4-methylphenyl)-2-(2-propyl-4-pyridinyl)thiazole; Q27166821; 2-(2-propyl-4-pyridyl)-4-(p-tolyl)thiazole;hydrobromide; 4-(4-methylphenyl)-2-(2-propyl-4-pyridinyl)thiazole;hydrobromide; 4-(4-METHYLPHENYL)-2-(2-PROPYL-4-PYRIDYL)-1,3-THIAZOLE

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Structure
Formula
C18H18N2S
IUPAC Name
4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole
Canonical SMILES
CCCC1=NC=CC(=C1)C2=NC(=CS2)C3=CC=C(C=C3)C
InChI
InChI=1S/C18H18N2S/c1-3-4-16-11-15(9-10-19-16)18-20-17(12-21-18)14-7-5-13(2)6-8-14/h5-12H,3-4H2,1-2H3
InChIKey
ZROSUBKIGBSZCG-UHFFFAOYSA-N
PubChem CID
1889993
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
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 Glioblastoma ICD-11: 2A00
Responsed Regulator RAC-alpha serine/threonine-protein kinase (AKT1) Suppressor
Pathway Response Cell adhesion molecules hsa04514
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3).

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Response regulation Fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
Responsed Regulator Serine/threonine-protein kinase mTOR (MTOR) Suppressor
Pathway Response Cell adhesion molecules hsa04514
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3).

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Response regulation Fatostatin induces ferroptosis by inhibiting the AKT/ mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
Responsed Regulator Serine/threonine-protein kinase mTOR (MTOR) Suppressor
Pathway Response Cell adhesion molecules hsa04514
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3).

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Response regulation Fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway.
References
Ref 1 Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. Cell Death Dis. 2023 Mar 25;14(3):211. doi: 10.1038/s41419-023-05738-8.