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

Article Details

Citation

Deng X, Wang J, Zhang J, Sim T, Kim ND, Sasaki T, Luther W 2nd, George RE, Janne PA, Gray NS

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. Epub 2011 Mar 15.

PubMed ID
21572589 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CrizotinibALK tyrosine kinase receptorIC 50 (nM)200N/AN/ADetails