Discovery of 3,5-diamino-1,2,4-triazole ureas as potent anaplastic lymphoma kinase inhibitors

Xianming Deng, Jinhua Wang, Jianming Zhang, Taebo Sim, Nam Doo Kim, Takaaki Sasaki, William Luther, Rani E. George, Pasi A. Jänne, Nathanael S. Gray

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)

    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 IC50 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.

    Original languageEnglish
    Pages (from-to)379-384
    Number of pages6
    JournalACS Medicinal Chemistry Letters
    Volume2
    Issue number5
    DOIs
    Publication statusPublished - 2011 May 12

    Keywords

    • 3,5-diamino-1,2,4-triazole urea
    • ALK

    ASJC Scopus subject areas

    • Biochemistry
    • Drug Discovery
    • Organic Chemistry

    Fingerprint

    Dive into the research topics of 'Discovery of 3,5-diamino-1,2,4-triazole ureas as potent anaplastic lymphoma kinase inhibitors'. Together they form a unique fingerprint.

    Cite this