Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX

  • ACS Med Chem Lett. 2017 Mar 1;8(4):423-427. doi: 10.1021/acsmedchemlett.7b00014.
John H Hutchinson  1 ,  Martin W Rowbottom  1 ,  David Lonergan  1 ,  Janice Darlington  1 ,  Pat Prodanovich  1 ,  Christopher D King  1 ,  Jilly F Evans  1 ,  Gretchen Bain  1
Affiliations
  • 1. PharmAkea Inc., 3030 Bunker Hill Street, Suite 300, San Diego, California 92109, United States.
PMID: 28435530 DOI: 10.1021/acsmedchemlett.7b00014
Abstract

Two series of novel LOXL2 enzyme inhibitors are described: benzylamines substituted with electron withdrawing groups at the para-position and 2-substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin-4-yl)methanamine 20 (hLOXL2 IC50 = 126 nM), was shown to be selective for LOXL2 over LOX and three Other amine oxidases (MAO-A, MAO-B, and SSAO). Compound 20 is the first published small molecule inhibitor selective for LOXL2 over LOX.

Keywords
(2-chloropyridin-4-yl)methanamine; LOXL2; fibrosis; inhibitor; lysyl oxidase-like 2.
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