2. Academic Validation
  3. Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors

Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors

  • ACS Med Chem Lett. 2011 May 12;2(5):379-384. doi: 10.1021/ml200002a.
Xianming Deng,  Jinhua Wang,  Jianming Zhang,  Taebo Sim,  Nam Doo Kim,  Takaaki Sasaki,  William Luther 2nd,  Rani E George,  Pasi A Jänne,  Nathanael S Gray
PMID: 21572589 DOI: 10.1021/ml200002a
Abstract

A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC(50) values of 70, 40, and 20 nM in Tel-ALK transformed Ba/F3 cells, respectively. Moreover, 15a and 23a potently inhibited the growth and survival of NPM-ALK positive anaplastic large cell lymphoma cell (SU-DHL-1) and neuroblastoma cell lines (KELLY, SH-SY5Y) containing the F1174L ALK mutation. These compounds provide novel leads for the development of small-molecule ALK inhibitors for Cancer therapy.

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