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) shows cytotoxicity with EC 50 of 23.5 μM in BT-474 cells and IC 50 of 30.14 μM, >100 μM for BT-474 and HMEC cells, respectively [1] [2]. ARN5187 (0-100 μM) activates the RevRE reporter in a concentration-dependent manner in HEK-293 cells [1]. ARN5187 (25, 50 μM) is a lysosomotropic-independent REV-ERB antagonistic activity [1]. ARN5187 (50 μM; 24 h) shows autophagy inhibition [1]. ARN5187 (50 μM; 2, 8, 24 h) effects autophagy formation and maturation [1]. Cell Cytotoxicity Assay [1] Cell Line: BT-474 cells Concentration: 0-100 μM Incubation Time: 48 h Result: Showed cytotoxicity with EC 50 of 23.5 μM. RT-PCR [1] Cell Line: BT-474 cells Concentration: 25, 50 μM Incubation Time: Result: Significantly enhanced the expression of BMAL1, PER1 and PEPCK in a dose-dependent manner. Western Blot Analysis [1] Cell Line: BT-474 cells Concentration: 50 μM Incubation Time: 24 h Result: Significantly increased the expression of α-LC3-II, α-p62, α-Cleaved PARP.