Discovery of cyclic guanidine-linked sulfonamides as inhibitors of LMTK3 kinase
作者: Maria A. OrtizHeather MichaelsBrandon MolinaSean ToenjesJennifer DavisGuya Diletta MarconiDavid HechtJeffrey L. GustafsonF. Javier PiedrafitaAdel Nefzi
作者单位: 1Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, United States
2Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL, United States
3San Diego State University, Department of Chemistry and Biochemistry, San Diego, CA, United States
4Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio, Cheti-Pescara, Via dei vestini, 31, Italy
5Southwestern College, Department of Chemistry, Chula Vista, CA, United States
6Florida International University, Miami, FL, United States
刊名: Bioorganic & Medicinal Chemistry Letters, 2020, Vol.30 (9)
来源数据库: Elsevier Journal
DOI: 10.1016/j.bmcl.2020.127108
关键词: LMTK3Small molecule kinase inhibitorsGuanidine-linked sulfonamideBreast cancerCombinatorial chemistrySolid-phase synthesis
英文摘要: Abstract(#br)Lemur tyrosine kinase 3 (LMTK3) is oncogenic in various cancers. In breast cancer, LMTK3 phosphorylates and modulates the activity of estrogen receptor-α (ERα) and is essential for the growth of ER-positive cells. LMTK3 is highly expressed in ER-negative breast cancer cells, where it promotes invasion via integrin β1. LMTK3 abundance and/or high nuclear expression have been linked to shorter disease free and overall survival time in a variety of cancers, supporting LMTK3 as a potential target for anticancer drug development. We sought to identify small molecule inhibitors of LMTK3 with the ultimate goal to pharmacologically validate this kinase as a novel target in cancer. We used a homogeneous time resolve fluorescence (HTRF) assay to screen a collection of mixture-based...
全文获取路径: Elsevier  (合作)
影响因子:2.338 (2012)

  • sulfonamides 磺胺类药物
  • linked 连接的
  • kinase 激酶
  • guanidine 
  • synthesis 合成
  • chemistry 化学
  • molecule 分子
  • cyclic 循环的
  • phase 相位
  • cancer 癌症