SGC-AAK1-1：一种靶向AAK1和BMP2K的化学探针。
SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K.
作者信息
Wells Carrow, Couñago Rafael M, Limas Juanita C, Almeida Tuanny L, Cook Jeanette Gowen, Drewry David H, Elkins Jonathan M, Gileadi Opher, Kapadia Nirav R, Lorente-Macias Alvaro, Pickett Julie E, Riemen Alexander, Ruela-de-Sousa Roberta R, Willson Timothy M, Zhang Cunyu, Zuercher William J, Zutshi Reena, Axtman Alison D
机构信息
Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.
Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States.
出版信息
ACS Med Chem Lett. 2019 Oct 23;11(3):340-345. doi: 10.1021/acsmedchemlett.9b00399. eCollection 2020 Mar 12.
Abstract
Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization furnished a small molecule chemical probe (SGC-AAK1-1, ) that is potent and selective for AAK1/BMP2K over other NAK family members, demonstrates narrow activity in a kinome-wide screen, and is functionally active in cells. This inhibitor represents one of the best available small molecule tools to study the functions of AAK1 and BMP2K.
摘要
合成了基于3-酰基氨基吲唑支架的抑制剂，以产生有效的双重AAK1/BMP2K抑制剂。优化得到了一种小分子化学探针（SGC-AAK1-1），它对AAK1/BMP2K具有比其他NAK家族成员更强的效力和选择性，在全激酶组筛选中显示出狭窄的活性，并且在细胞中具有功能活性。这种抑制剂是研究AAK1和BMP2K功能的最佳可用小分子工具之一。
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