Abstract 3580: Discovery and SAR study of a novel and potent Itk inhibitor as a targeted therapeutic agent for T-cell lymphoma and leukemia

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 3580
• Main Authors: Liu, Ruiwu, Guo, Wenchang, Ma, Aihong, Sanchez, Eduardo, Wang, Yan, Li, Jixian, Xu, Chunping, Ning, Jinying, Huang, Wenzhe, Mazloom, Anisha, Song, Aimin, Lam, Kit S., Xia, Michelle, Chen, Yiyou, Kung, Hsing-Jien
• Format: Journal Article
• Language: English
• Published: 15-04-2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-3580

Abstract
Itk (IL2-inducible T-cell kinase) is a non-receptor protein tyrosine kinase. It is selectively expressed in T cells, Mast cells, and NK cells. It plays an important role in T-cell maturation, proliferation, and malignancies. Using Western blotting, Itk was only detected in three T-cell lymphoma and leukemia cell lines (Jurkat, Molt-4, and Hut78) out of 41 different cancer cell lines. A small molecule named CTA056 showed potent and selective inhibition of Itk kinase activity and growth in each of the three T-cell cancer cell lines. After treatment of Jurkat cells with CTA056, Itk phosphorylation was inhibited in a dose-dependent manner. In addition, apoptosis was induced in Jurkat cells following treatment with CTA056. In order to better understand structure-activity relationship (SAR) on CTA056, a series of analogs of CTA056 were designed, synthesized, and tested for their inhibition of both Itk phosphorylation and cancer cell growth. Several analogs showed better activity and selectivity. The results will be presented. Success in this endeavor could lead to the development of novel targeted therapy, rather than traditional chemotherapy, for T-cell lymphomas and leukemia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3580. doi:10.1158/1538-7445.AM2011-3580