retinoic acid receptor rars antagonists agn 193109  (MedChemExpress)

Journal: Redox Biology

Article Title: Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis

doi: 10.1016/j.redox.2024.103361

Figure Lengend Snippet: ALDH1A1 inhibits ferroptosis through detoxifying aldehydes, promoting production of NADH and improving RARA function . (A – D) Measurement of retinal (A), 4-HNE (B), retinoic acid (C), and NADH (D) production in MIAPACA3 and H2122 cells with ALDH1A1 NC, inhibitor (CM10:500 nM), KO and OE under sotorasib or adagrasib treatment (IC50,IC90, Peak serum concentration, 72 h) (n = 3). (E) Relative viability showed retinoic acid receptor α (RARA) resisted KRAS G12C mutant cells to ferroptosis caused by RSL3, IKE, sotorasib and adagtasib (IC50), demonstrated by medications with RARA inhibitors AGN193109 (1000 nM) or activator ATRA (1000 nM) for 72 h. (n = 3) (F) Lipid peroxidation of KRAS G12C mutant cells increased when added AGN193109 (1000 nM) to sotorasib or adagrasib (IC50) for 72 h. (n = 3) (G) Dual-luciferase assays reflected significant RARA activity depression in ALDH1A1 -KO and CM10 (500 nM) treated groups (MIAPACA2 and H2122 cells) under KRAS G12C inhibitors medications (IC50). (n = 3) Data were analyzed by Student's t-test and were presented by mean ± SD.

Article Snippet: Pan-KRAS inhibitor BI-2493, RARA inhibitor AGN193109, and MNK inhibitor ECT-206 were purchased from MedChemExpress (Shanghai, China).

Techniques: Concentration Assay, Mutagenesis, Medications, Luciferase, Activity Assay