Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0416)
Name
(6R,6aR,9S,11bS,14R)-4,4-Dimethyl-8-methylene-7,11,12-trioxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl valinate
Drug Type
Small molecule
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
Cell proliferation
In Vitro Model HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
BGC-823 cells Gastric carcinoma Homo sapiens CVCL_3360
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
GES-1 cells Normal Homo sapiens CVCL_EQ22
In Vivo Model
Male nude mice (ages 6-8 weeks) used in the studies were purchased from Hunan SJA Laboratory Animal Co. (Changsha, China). Male nude mice were subcutaneously injected with MGC-803cells into the right flank of mouse. Once the tumor volume reached 100-200 mm3, mice were randomly divided into 5 groups (6 mice/group) and administered with saline,a2(5, 10, and 20 mg/kg), or 5-fluorouracil (5-FU, 15mg/kg) once a day for 21 daysviatail vein injection.

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Response regulation (6R,6aR,9S,11bS,14R)-4,4-Dimethyl-8-methylene-7,11,12-trioxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl valinate (a2), a new JDA derivative, inhibited the growth of gastric cancer cells. Importantly, compounda2decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity ofa2. Furthermore, a2caused ferrous iron accumulation through the autophagy pathway, prevention of which rescueda2induced ferrous iron elevation and cell growth inhibition.
References
Ref 1 Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer. Acta Pharm Sin B. 2021 Jun;11(6):1513-1525. doi: 10.1016/j.apsb.2021.05.006. Epub 2021 May 13.