GSK1362 is a selective inverse agonist of REV-ERB. It disrupts the interaction between REV-ERBα and corepressors (NCoR1, SMRT2, RIP140). By enhancing the transcription of BMAL1, GSK1362 acts as an inverse agonist, counteracting endogenous REV-ERB ligands that inhibit BMAL1. GSK1362 suppresses the expression of inflammation factors induced by LPS and inhibits IL-1β-induced Cxcl5 transcription in cells. It is utilized in the study of inflammatory diseases.

GSK1362 acts as a reverse agonist by increasing transcription in a concentration-dependent manner in HEK293 cells co-transfected with HA-Rev-Erbα and Bmal1-Luc reporter genes, thereby alleviating the inhibition of BMAL1 by endogenous REV-ERB ligands. At 10 μM for 4 hours, GSK1362 suppresses the production of various LPS-induced inflammatory factors in alveolar macrophages collected at ZT8. Additionally, at 10 μM for 16 hours, it inhibits the induction of Cxcl5 transcription in serum shock-synchronized mouse LA-4 cells. GSK1362 also significantly increases the abundance of REV-ERBα protein in serum shock-synchronized human primary bronchial epithelial (NHBE) cells when administered at 10 μM for 4 hours. Furthermore, pretreatment with 10 μM GSK1362 for 15 minutes stabilizes REV-ERBα protein, counteracting IL-1β-induced protein degradation in synchronized NHBE cells. Lastly, GSK1362 at 10 μM for 4 hours blocks IL-1β or TNF-α-induced ubiquitination of REV-ERBα in HEK293T cells transfected with HA-Rev-Erbα, His-Ub, and SENP-1 plasmids.