Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00079)
Name
Thromboembolic stroke
ICD
ICD-11: 8B20
Full List of Target(s) of This Ferroptosis-centered Disease
Heme oxygenase 1 (HMOX1)
 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 Driver/Suppressor
Responsed Disease Thromboembolic stroke [ICD-11: 8B20]
Responsed Drug ADA-409-052 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model BV-2 cells Normal Mus musculus CVCL_0182
Neuro-2a cells Neuroblastoma Mus musculus CVCL_0470
RAW 264.7 cells Leukemia Mus musculus CVCL_0493
In Vivo Model
Brain penetration study was carried out by TCG Lifesciences Ltd (Kolkata, India) in male BALB/c mice (6-8 weeks old; 18-20 g, in-house breeding). Mice were housed individually under 12/12 h lightdark cycle with free access to food and water. In two experiments 10 mg/kg or 30 mg/kg of ADA-409-052 (HPLC Purity: 99.7%) dissolved in Tween-80 (0.5%, Merck, Germany) -methylcellulose (Sigma) solution was administered as a single bolus by oral gavage (p.o.). ADA-409-052- or vehicle-administered mice were sacrificed 0.75, 4, and 24 h later (n = 3/group).

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Response regulation ADA-409-052 inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. In addition, ADA-409-052 reduced the expression of stroke-induced Hmox1.
References
Ref 1 An arylthiazyne derivative is a potent inhibitor of lipid peroxidation and ferroptosis providing neuroprotection in vitro and in vivo. Sci Rep. 2021 Feb 10;11(1):3518. doi: 10.1038/s41598-021-81741-3.