Ferroptosis Regulator Information
General Information of the Ferroptosis Regulator (ID: REG10087)
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AR
can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
| In total 2 item(s) under this target | |||||
| Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
| Target for Ferroptosis | Suppressor | ||||
| Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
| Responsed Drug | ALZ003 | Investigative | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Apoptosis | hsa04210 | ||||
| Ubiquitin mediated proteolysis | hsa04120 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| Cell proliferation | |||||
In Vitro Model |
U-87MG cells | Glioblastoma | Homo sapiens | CVCL_GP63 | |
| A-172 cells | Glioblastoma | Homo sapiens | CVCL_0131 | ||
| In Vivo Model |
NOD-SCID male mice (8-week-old) were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). For glioblastoma and TMZ-resistant glioblastoma transplantation, luciferase-expressed U87MG cells (2 x 105) and U87MG-R cells (2 x 105) were injected into the cortex, respectively, at the depth of 3 mm using stereotactic guidance and microprocessor single syringe (Harvard Apparatus, Holliston, MA, USA). After 10 days of transplantation, TMZ (15 mg/kg) and ALZ003 were orally and intravenously administrated three times per week, respectively.
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| Response regulation | ALZ003 targeting AR for degradation strongly exhibits the therapeutic effect on glioblastoma, including TMZ-resistant tumor,in vitroandin vivo. Particularly, GPX4 was positively regulated by AR, and overexpression of AR also prevented lipid peroxidation. | ||||
| Experiment 2 Reporting the Ferroptosis Target of This Regulator | [2] | ||||
| Target for Ferroptosis | Suppressor | ||||
| Responsed Disease | Kidney injury | ICD-11: NB92 | |||
| Responsed Drug | Furosine dihydrochloride | Investigative | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Cell Process | Cell ferroptosis | ||||
In Vitro Model |
mPKCs (Mouse primary kidney cells) | ||||
| In Vivo Model |
A total of 60 ICR female mice (20 ± 2g, 5 mice/group) were divided into 12 groups (control and 10 furosine treatment groups). Furosine was dissolved in distilled water and a dose of 0.24 g/kg b.w. was administered by gavage or tail vein injection (0.2 mL volume per mouse) once at the beginning. This dose was chosen based on the median lethal dose (LD50) determined in previous acute toxicity experiments, in which the LD50 of furosine was 1.6 g/kg b.w. Mice were fasted for 4 h prior to dosing; animals were sacrificed at 0 (controls), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after administration, and kidney tissue was dissected and blood samples were collected.
Click to Show/Hide
|
||||
| Response regulation | Furosine might decrease the activity of GPX4 via AR, thereby disrupting the conversion of peroxides into non-toxic reduced forms. Once GPX4 loses its reduction activity, excessivelipid peroxidationin kidney cells can lead to cell death by ferroptosis. To conclude, the study demonstrated for the first time the toxicity of furosine toward kidney injury. | ||||
Glioblastoma [ICD-11: 2A00]
| In total 1 item(s) under this disease | |||||
| Experiment 1 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
| Target Regulator | Androgen receptor (AR) | Protein coding | |||
| Responsed Drug | ALZ003 | Investigative | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Apoptosis | hsa04210 | ||||
| Ubiquitin mediated proteolysis | hsa04120 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| Cell proliferation | |||||
In Vitro Model |
U-87MG cells | Glioblastoma | Homo sapiens | CVCL_GP63 | |
| A-172 cells | Glioblastoma | Homo sapiens | CVCL_0131 | ||
| In Vivo Model |
NOD-SCID male mice (8-week-old) were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). For glioblastoma and TMZ-resistant glioblastoma transplantation, luciferase-expressed U87MG cells (2 x 105) and U87MG-R cells (2 x 105) were injected into the cortex, respectively, at the depth of 3 mm using stereotactic guidance and microprocessor single syringe (Harvard Apparatus, Holliston, MA, USA). After 10 days of transplantation, TMZ (15 mg/kg) and ALZ003 were orally and intravenously administrated three times per week, respectively.
Click to Show/Hide
|
||||
| Response regulation | ALZ003 targeting AR for degradation strongly exhibits the therapeutic effect on glioblastoma, including TMZ-resistant tumor,in vitroandin vivo. Particularly, GPX4 was positively regulated by AR, and overexpression of AR also prevented lipid peroxidation. | ||||
Kidney injury [ICD-11: NB92]
| In total 1 item(s) under this disease | |||||
| Experiment 1 Reporting the Ferroptosis-centered Disease Response | [2] | ||||
| Target Regulator | Androgen receptor (AR) | Protein coding | |||
| Responsed Drug | Furosine dihydrochloride | Investigative | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Cell Process | Cell ferroptosis | ||||
In Vitro Model |
mPKCs (Mouse primary kidney cells) | ||||
| In Vivo Model |
A total of 60 ICR female mice (20 ± 2g, 5 mice/group) were divided into 12 groups (control and 10 furosine treatment groups). Furosine was dissolved in distilled water and a dose of 0.24 g/kg b.w. was administered by gavage or tail vein injection (0.2 mL volume per mouse) once at the beginning. This dose was chosen based on the median lethal dose (LD50) determined in previous acute toxicity experiments, in which the LD50 of furosine was 1.6 g/kg b.w. Mice were fasted for 4 h prior to dosing; animals were sacrificed at 0 (controls), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after administration, and kidney tissue was dissected and blood samples were collected.
Click to Show/Hide
|
||||
| Response regulation | Furosine might decrease the activity of GPX4 via AR, thereby disrupting the conversion of peroxides into non-toxic reduced forms. Once GPX4 loses its reduction activity, excessivelipid peroxidationin kidney cells can lead to cell death by ferroptosis. To conclude, the study demonstrated for the first time the toxicity of furosine toward kidney injury. | ||||
ALZ003
[Investigative]
| In total 1 item(s) under this drug | |||||
| Experiment 1 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
| Drug for Ferroptosis | Inducer | ||||
| Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
| Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Apoptosis | hsa04210 | ||||
| Ubiquitin mediated proteolysis | hsa04120 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| Cell proliferation | |||||
In Vitro Model |
U-87MG cells | Glioblastoma | Homo sapiens | CVCL_GP63 | |
| A-172 cells | Glioblastoma | Homo sapiens | CVCL_0131 | ||
| In Vivo Model |
NOD-SCID male mice (8-week-old) were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). For glioblastoma and TMZ-resistant glioblastoma transplantation, luciferase-expressed U87MG cells (2 x 105) and U87MG-R cells (2 x 105) were injected into the cortex, respectively, at the depth of 3 mm using stereotactic guidance and microprocessor single syringe (Harvard Apparatus, Holliston, MA, USA). After 10 days of transplantation, TMZ (15 mg/kg) and ALZ003 were orally and intravenously administrated three times per week, respectively.
Click to Show/Hide
|
||||
| Response regulation | ALZ003 targeting AR for degradation strongly exhibits the therapeutic effect on glioblastoma, including TMZ-resistant tumor,in vitroandin vivo. Particularly, GPX4 was positively regulated by AR, and overexpression of AR also prevented lipid peroxidation. | ||||
Furosine dihydrochloride
[Investigative]
| In total 1 item(s) under this drug | |||||
| Experiment 1 Reporting the Ferroptosis-centered Drug Response | [2] | ||||
| Drug for Ferroptosis | Inducer | ||||
| Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
| Responsed Disease | Kidney injury | ICD-11: NB92 | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Cell Process | Cell ferroptosis | ||||
In Vitro Model |
mPKCs (Mouse primary kidney cells) | ||||
| In Vivo Model |
A total of 60 ICR female mice (20 ± 2g, 5 mice/group) were divided into 12 groups (control and 10 furosine treatment groups). Furosine was dissolved in distilled water and a dose of 0.24 g/kg b.w. was administered by gavage or tail vein injection (0.2 mL volume per mouse) once at the beginning. This dose was chosen based on the median lethal dose (LD50) determined in previous acute toxicity experiments, in which the LD50 of furosine was 1.6 g/kg b.w. Mice were fasted for 4 h prior to dosing; animals were sacrificed at 0 (controls), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after administration, and kidney tissue was dissected and blood samples were collected.
Click to Show/Hide
|
||||
| Response regulation | Furosine might decrease the activity of GPX4 via AR, thereby disrupting the conversion of peroxides into non-toxic reduced forms. Once GPX4 loses its reduction activity, excessivelipid peroxidationin kidney cells can lead to cell death by ferroptosis. To conclude, the study demonstrated for the first time the toxicity of furosine toward kidney injury. | ||||
References