Development of a potent and selective cell penetrant Legumain inhibitor. Issue 23 (1st December 2015)

• Record Type: Journal Article
• Authors: Ness, Kerry A.; Eddie, Sharon L.; Higgins, Catherine A.; Templeman, Amy; D'Costa, Zenobia; Gaddale, Kishore K.D.; Bouzzaoui, Samira; Jordan, Linda; Janssen, Dominic; Harrison, Timothy; Burkamp, Frank; Young, Andrew; Burden, Roberta; Scott, Christopher J.; Mullan, Paul B.; Williams, Rich
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 23(2015)
• Page Start: 5642
• Page End: 5645
• Publication Date: 2015-12-01
• Subjects: Legumain -- Cancer -- Cyano warhead -- Cellular active inhibitor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.10.001
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2–P3 linker units and the P3 group SAR which led to the identification of10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that10t has activity in both cancer cell viability and colony formation assays.