ARN5187 is a lysosomal compound, REV-ERB β Ligand. ARN5187 inhibits REV-ERB-mediated transcriptional regulation and autophagy. ARN5187 shows lysosomal efficacy and cytotoxicity, and can induce apoptosis.

ARN5187 (compound 1) (0-100 μM; 48 h) demonstrates cytotoxicity with an EC50 of 23.5 μM in BT-474 cells and IC50 values of 30.14 μM and >100 μM in BT-474 and HMEC cells, respectively [1][2]. In HEK-293 cells, ARN5187 (0-100 μM) activates the RevRE reporter in a concentration-dependent manner [1]. ARN5187 (25, 50 μM) exhibits lysosomotropic-independent REV-ERB antagonistic activity [1], and at 50 μM (24 h), it shows autophagy inhibition and affects autophagy formation and maturation [1]. In BT-474 cells, ARN5187 significantly enhances the expression of BMAL1, PER1, and PEPCK in a dose-dependent manner (25, 50 μM), and at 50 μM (24 h), significantly increases the expression of α-LC3-II, α-p62, and α-Cleaved PARP [1].