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
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.
ACS Med Chem Lett. 2019 Oct 23;11(3):340-345. doi: 10.1021/acsmedchemlett.9b00399. eCollection 2020 Mar 12.
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.
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。
