Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0391)
| Name |
R46A2
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|---|---|---|---|---|---|
| Drug Type |
Others
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Full List of Ferroptosis Target Related to This Drug
Unspecific Target
| In total 2 item(s) under this Target | |||||
| Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [1] | ||||
| Responsed Disease | Health | ICD-11: N.A. | |||
| Responsed Regulator | Mitogen-activated protein kinase 8 (MAPK8) | Driver | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Ferroptosis | hsa04216 | ||||
| Cell Process | Cell ferroptosis | ||||
| In Vitro Model | hHCs (Hippocampal cells) | ||||
| In Vivo Model |
Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days.
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| Response regulation | Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK ( MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. | ||||
| Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target | [1] | ||||
| Responsed Disease | Health | ICD-11: N.A. | |||
| Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Ferroptosis | hsa04216 | ||||
| Cell Process | Cell ferroptosis | ||||
| In Vitro Model | hHCs (Hippocampal cells) | ||||
| In Vivo Model |
Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days.
Click to Show/Hide
|
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| Response regulation | Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. | ||||