小分子赖氨酰氧化酶样2（LOXL2）抑制剂：一种对LOXL2具有选择性而非LOX的抑制剂的鉴定。
Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX.
作者信息
Hutchinson John H, Rowbottom Martin W, Lonergan David, Darlington Janice, Prodanovich Pat, King Christopher D, Evans Jilly F, Bain Gretchen
机构信息
PharmAkea Inc., 3030 Bunker Hill Street, Suite 300, San Diego, California 92109, United States.
出版信息
ACS Med Chem Lett. 2017 Mar 1;8(4):423-427. doi: 10.1021/acsmedchemlett.7b00014. eCollection 2017 Apr 13.
Abstract
Two series of novel LOXL2 enzyme inhibitors are described: benzylamines substituted with electron withdrawing groups at the -position and 2-substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin-4-yl)methanamine (hLOXL2 IC = 126 nM), was shown to be selective for LOXL2 over LOX and three other amine oxidases (MAO-A, MAO-B, and SSAO). Compound is the first published small molecule inhibitor selective for LOXL2 over LOX.
摘要
描述了两类新型赖氨酰氧化酶2（LOXL2）酶抑制剂：在α位被吸电子基团取代的苄胺和2-取代吡啶-4-基甲胺。最有效的化合物（2-氯吡啶-4-基）甲胺（人LOXL2的半数抑制浓度[IC] = 126 nM）对LOXL2具有选择性，相对于赖氨酰氧化酶（LOX）以及其他三种胺氧化酶（单胺氧化酶A[MAO-A]、单胺氧化酶B[MAO-B]和二胺氧化酶[SSAO]）。化合物是首个发表的对LOXL2比对LOX具有选择性的小分子抑制剂。
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