L001 is a potent and selective EP4 antagonist with cAMP IC50 of 7.29 nM, impairs pancreatic cancer migration and invasion.
L001 is superior to E7046 in CRE reporter assay (IC50=40.6 nM).
L001 blocks PGE2-induced EP4/β-arrestin2 interaction with an IC50 value of 0.16 nM in TANGO assay, significantly blocks the PGE2-induced phosphorylation of ERK1/2 in a dose-dependent manner.
L001 exhibits a >600-fold greater selectivity in human EP4 than the other prostaglandin E receptors (IC50 > 10 µM for EP1, EP2 and EP3).
L001 is a potent EP4 antagonist in human, monkey, mouse and rat as detected by the calcium flux assay with IC50 values of 1.47 nM, 5.24 nM, 3.20 nM and 14.25 nM, respectively.
L001 (10 uM) affects PGE2-induced pancreatic cancer cell migration using the wound healing assay and transwell assay.
L001 abrogates Hippo-YAP activation and pro-metastatic factors expression in pancreatic cancer cells.
L001 treatment (75 mg/kg/day) impairs hepatic metastasis of pancreatic cancer in vivo.