ML191

ML191 (CID23612552) is a GPR55 antagonist. ML191 inhibits ERK phosphorylation and PKC β II translocation downstream of GPR55 signaling. ML191 suppresses LPI-induced activation of ERK1/2 and p38 MAPK signaling, blocks the transcription of RANKL-induced osteoclastogenesis markers, and reduces the bone resorption activity of mature osteoclasts promoted by RANKL. ML191 can be used to investigate diseases associated with bone degradation caused by excessive osteoclast activation, such as osteoporosis and bone damage during the formation stage of bone metastases^[1][2]. In Vitro:ML191 (0.06-32 µM; 30-75 min) potently inhibits GPR55-mediated β-arrestin translocation in U2OS cells, with an IC₅₀ of 1.08 µM. It exhibits over 29-fold selectivity over GPR35 and CB2, and only weak selectivity for the CB1 receptor^[1].
ML191 (10-30 µM) inhibits GPR55-mediated PKCβII translocation in HEK293 cells, with the maximum inhibitory effect observed at 30 µM^[1].
ML191 inhibits GPR55-mediated ERK1/2 phosphorylation in GPR55-expressing cells, with an EC₅₀ of 0.143 µM^[1].
ML191 (30 µM; 10 min pre-incubation, 10 min LPI stimulation) potently inhibits LPI-induced phosphorylation of ERK2 and p38 in shCTRL-HeLa cells, reducing the LPI-activated ERK2 level to 1.8-fold of the basal level and the p38 activation level to 1.2-fold of the basal level at 10 min post stimulation^[2].
ML191 (0.5 µM; 72 h) inhibits RANKL-induced osteoclast maturation in RAW264.7 cells, reduces the mRNA levels of key osteoclastogenic markers (Nfatc1, Cathepsin-k, Mmp-9, Trap) by 30%-70%, and increases the mRNA level of Gpr55 to 46.1 times that of undifferentiated cells after 72 h of treatment^[2].
ML191 (0.5 µM; 7 days) inhibits the bone resorption activity of mature osteoclasts differentiated from RAW264.7 cells, and reduces the total bone erosion area by 30% after 7 days of RANKL treatment^[2].