rar antagonist agn193109  (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

Journal: Genome Biology

Article Title: Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm

doi: 10.1186/s13059-024-03354-z

Figure Lengend Snippet: Multi-omics data integration allows to infer a PE-specific transcription factor network. A Heatmaps showing RARA ChIP-Seq and ATAC-Seq signal, measured in AFE (d5 -RA) and PE (d5 +RA) cells, within 3 kb-long regions centered on the summits of Enriched, Equal, and Depleted RARA-ChIP-Seq peaks. ChIP-Seq Signal was calculated as log2-transformed fold change of the RPGC values of IP over input, with a bin size of 50 bp. ATAC-Seq Signal was calculated on merged replicates as RPGC values with a bin size of 50 bp. Summary plots reporting the position-specific average signal calculated for each cell type and peak category are shown on top. B PE-specific TF-TF activation network. Nodes represent TFs that are specifically active and upregulated in PE (d5 +RA) with respect to DE (d2). Thin directed edges indicate the presence of a Gain ATAC-Seq peak harboring a source TF-specific FP located less than 25 kb from the TSS of the target TF; their color reflects the minimum distance between the target TSS and a Gain peak with a source-specific FP. Thick directed black edges connect RARA to its TF targets, identified via ChIP-Seq. Node color intensity is proportional to the log2(FC) in the expanded AFE vs PE comparison. See also Additional File . C Heatmap showing the expression in AFE (d5 -RA), PE-RAi (d5 +RA +AGN193109), and PE (d5 +RA) samples from Differentiation_2 experiment (see ) of the TFs belonging to the TFN, stratified based on their dependence on RA. Hierarchical clustering within each group is also shown. The expression values reported in the heatmap correspond to row-scaled (Z-score) rlog-transformed count data with batch effect correction

Article Snippet: To inhibit the response to Retinoic Acid during differentiation, we performed an independent differentiation experiment in triplicate (Differentiation_2) to derive, in addition to AFE (d5 -RA) and PE cells (d5 +RA), a cellular type named PE-RAi (d5 +RA +AGN193109), obtained by adding the pan-Retinoic Acid Receptor antagonist AGN193109 (Tocris, 5758) in a concentration of 50 nM to the CDM2 medium with A-83–01, 1uM and DM3189, 250 nM, on day3 of differentiation, and collecting the cells at day 5.

Techniques: Biomarker Discovery, ChIP-sequencing, Transformation Assay, Activation Assay, Comparison, Expressing