One of the known mechanisms of PC6 action in regulating endometrial epithelial cell receptivity is through the cleavage of pro-integrin-aV into its functional heavy and light chains. To further establish that MCE Company 1454585-06-8 compound 1o reduced Ishikawa cell receptivity to spheroid attachment through PC6 inhibition, total cell proteins were AMG 900 analysed for pro-integrin-aV cleavage by western blot. Although both the proform and the heavy chain of integrin-aV were detected in all cell lysates, the relative amount of each form was clearly different between control and compound 1o-treated cells. The heavy chain was reduced whereas the pro-integrin-aV was increased in cells treated with compound 1o compared with controls. This is consistent with PC6 cleavage of the pro-integrin-aV into its functional forms being inhibited by compound 1o. This study identified compound 1o as the most potent synthetic small molecule PC6 inhibitor to inhibit PC6-dependent cellular processes essential for embryo implantation. Our previous publication showed C-30k-PEG Poly R as a potent peptide-based PC6 inhibitor. We thus compared these two different types of PC6 inhibitors compound 1o and C-30k-PEG Poly R, for their potency in inhibiting stromal cell decidualization and epithelial receptivity. While both equally inhibited decidualisation of HESCs in a dose-dependent manner, C-30k-PEG Poly R was significantly less potent than compound 1o in inhibiting Ishikawa cell receptivity to JAR spheroids. Compound 1o inhibited spheroid attachment in a clear dose-dependent manner, and was significantly more inhibitory than C-30k-PEG Poly R. PC6 plays a crucial role in embryo implantation and HIV infection; it is therefore highly desirable to develop inhibitors of PC6 for potential non-hormonal female contraceptives that could also protect women from HIV. In the ongoing search for PC6 inhibitors with appropriate physiochemical characteristics for therapeutic applications, we investigated five synthetic small molecule compounds that had been previously reported as inhibitors of furin, another PC member. Our studies revealed that all five compounds were potent inhibitors against rhPC6 in vitro and they were able to adopt similar binding modes in the hP
