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

[Image: see text] 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, respectiv...

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Autores principales: Deng, Xianming, Wang, Jinhua, Zhang, Jianming, Sim, Taebo, Kim, Nam Doo, Sasaki, Takaaki, Luther, William, George, Rani E., Jänne, Pasi A., Gray, Nathanael S.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2011
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093683/
https://www.ncbi.nlm.nih.gov/pubmed/21572589
http://dx.doi.org/10.1021/ml200002a
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author Deng, Xianming
Wang, Jinhua
Zhang, Jianming
Sim, Taebo
Kim, Nam Doo
Sasaki, Takaaki
Luther, William
George, Rani E.
Jänne, Pasi A.
Gray, Nathanael S.
author_facet Deng, Xianming
Wang, Jinhua
Zhang, Jianming
Sim, Taebo
Kim, Nam Doo
Sasaki, Takaaki
Luther, William
George, Rani E.
Jänne, Pasi A.
Gray, Nathanael S.
author_sort Deng, Xianming
collection PubMed
description [Image: see text] 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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spelling pubmed-30936832011-05-13 Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors Deng, Xianming Wang, Jinhua Zhang, Jianming Sim, Taebo Kim, Nam Doo Sasaki, Takaaki Luther, William George, Rani E. Jänne, Pasi A. Gray, Nathanael S. ACS Med Chem Lett [Image: see text] 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. American Chemical Society 2011-03-15 /pmc/articles/PMC3093683/ /pubmed/21572589 http://dx.doi.org/10.1021/ml200002a Text en Copyright © 2011 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Deng, Xianming
Wang, Jinhua
Zhang, Jianming
Sim, Taebo
Kim, Nam Doo
Sasaki, Takaaki
Luther, William
George, Rani E.
Jänne, Pasi A.
Gray, Nathanael S.
Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title_full Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title_fullStr Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title_full_unstemmed Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title_short Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
title_sort discovery of 3,5-diamino-1,2,4-triazole ureas as potent anaplastic lymphoma kinase inhibitors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093683/
https://www.ncbi.nlm.nih.gov/pubmed/21572589
http://dx.doi.org/10.1021/ml200002a
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