2. Academic Validation
  3. Identification and SAR exploration of a novel series of Legumain inhibitors

Identification and SAR exploration of a novel series of Legumain inhibitors

  • Bioorg Med Chem Lett. 2019 Jun 15;29(12):1546-1548. doi: 10.1016/j.bmcl.2019.03.019.
Sharon L Eddie 1,  Aaron Gregson 1,  Emma Graham 1,  Stephanie Burton 2,  Timothy Harrison 2,  Roberta Burden 3,  Christopher J Scott 3,  Paul B Mullan 1,  Rich Williams 4
Affiliations

Affiliations

  • 1 CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, United Kingdom.
  • 2 Almac Discovery, Health Sciences Building, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7AE, United Kingdom.
  • 3 School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, United Kingdom.
  • 4 CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, United Kingdom. Electronic address: rich.williams@qub.ac.uk.
PMID: 31005445 DOI: 10.1016/j.bmcl.2019.03.019
Abstract

This letter describes the development of a series of potent and selective small molecule Legumain inhibitors suitable as chemical probes for in vitro experiments. Our previous research had identified a dipeptide inhibitor utilizing a semi-reversible cyano warhead that generated 2, a cell active inhibitor. This work explores an alternative P2-P3 linker and further SAR exploration of the P3 group which led to the identification of 16i, a highly potent inhibitor with excellent physiochemical properties.

Keywords

Legumain; SAR; Small molecule inhibitor.

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