89939-36-6Relevant articles and documents
Improving the Selectivity of PACE4 Inhibitors through Modifications of the P1 Residue
Dianati, Vahid,Navals, Pauline,Couture, Frédéric,Desjardins, Roxane,Dame, Anthony,Kwiatkowska, Anna,Day, Robert,Dory, Yves L.
, p. 11250 - 11260 (2019/01/04)
Paired basic amino acid cleaving enzyme 4 (PACE4), a serine endoprotease of the proprotein convertases family, has been recognized as a promising target for prostate cancer. We previously reported a selective and potent peptide-based inhibitor for PACE4, named the multi-Leu peptide (Ac-LLLLRVKR-NH2 sequence), which was then modified into a more potent and stable compound named C23 with the following structure: Ac-dLeu-LLLRVK-Amba (Amba: 4-amidinobenzylamide). Despite improvements in both in vitro and in vivo profiles of C23, its selectivity for PACE4 over furin was significantly reduced. We examined other Arg-mimetics instead of Amba to regain the lost selectivity. Our results indicated that the replacement of Amba with 5-(aminomethyl)picolinimidamide increased affinity for PACE4 and restored selectivity. Our results also provide a better insight on how structural differences between S1 pockets of PACE4 and furin could be employed in the rational design of selective inhibitors.
Acylated benzylmaltosides as inhibitors of smooth muscle cell proliferation
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Page/Page column 9-10, (2008/06/13)
This invention provides smooth muscle cell proliferation inhibitors of formula I having the structure wherein R1, R2, R3, R4, and R5 are each, independently, hydrogen, acyl of 2-7 carbon atoms, haloac
