ARN5187 trihydrochloride

ARN5187 trihydrochloride is a lysosomotropic REV-ERBβ ligand with a dual inhibitory activity toward REV-ERB-mediated transcriptional regulation and autophagy. ARN5187 trihydrochloride shows lysosomotropic potency and cytotoxicity. ARN5187 trihydrochloride induces apoptosis[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

REV-ERBβ[1]

ARN5187 trihydrochloride (compound 1) (0-100 µM; 48 h) shows cytotoxicity with EC50 of 23.5 µM in BT-474 cells and IC50 of 30.14 µM, >100 µM for BT-474 and HMEC cells, respectively[1][2]. ARN5187 trihydrochloride (0-100 µM) activates the RevRE reporter in a concentration-dependent manner in HEK-293 cells[1]. ARN5187 trihydrochloride (25, 50 µM) is a lysosomotropic-independent REV-ERB antagonistic activity[1]. ARN5187 trihydrochloride (50 µM; 24 h) shows autophagy inhibition[1]. ARN5187 trihydrochloride (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 EC50 of 23.5 µM. 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. 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.

[1]. De Mei C, et al. Dual inhibition of REV-ERBβ and autophagy as a novel pharmacological approach to induce cytotoxicity in cancer cells. Oncogene. 2015 May 14;34(20):2597-608.

[2]. Torrente E, et al. Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy. J Med Chem. 2015 Aug 13;58(15):5900-15.