Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00049)
Name
Neuroblastoma
ICD
ICD-11: 2D50
Full List of Target(s) of This Ferroptosis-centered Disease
Transferrin receptor protein 1 (TFRC)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Pediatric neuroblastoma [ICD-11: 2D50]
Responsed Regulator N-myc proto-oncogene protein (MYCN) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model SH-EP cells Neuroblastoma Homo sapiens CVCL_0524
SK-N-AS cells Neuroblastoma Homo sapiens CVCL_1700
SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
Response regulation Pediatric neuroblastoma (NB) cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Neuroblastoma [ICD-11: 2D50]
Responsed Drug Fer-1 analogue 37 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model IMR-32 cells Neuroblastoma Homo sapiens CVCL_0346
In Vivo Model
All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled.

    Click to Show/Hide
Response regulation The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Neuroblastoma [ICD-11: 2D50]
Responsed Drug Fer-1 analogue 38 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model IMR-32 cells Neuroblastoma Homo sapiens CVCL_0346
In Vivo Model
All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled.

    Click to Show/Hide
Response regulation The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Neuroblastoma [ICD-11: 2D50]
Responsed Drug Fer-1 analogue 39 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model IMR-32 cells Neuroblastoma Homo sapiens CVCL_0346
In Vivo Model
All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled.

    Click to Show/Hide
Response regulation The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice.
References
Ref 1 MYCN mediates TFRC-dependent ferroptosis and reveals vulnerabilities in neuroblastoma. Cell Death Dis. 2021 May 19;12(6):511. doi: 10.1038/s41419-021-03790-w.
Ref 2 Discovery of Novel, Drug-Like Ferroptosis Inhibitors with in Vivo Efficacy. J Med Chem. 2018 Nov 21;61(22):10126-10140. doi: 10.1021/acs.jmedchem.8b01299. Epub 2018 Nov 6.