NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3.

ABSTRACT:

Background

Human or animals lacking either JAK3 or the common gamma chain (gammac) expression display severe combined immunodeficiency disease, indicating the crucial role of JAK3 in T-cell development and the homeostasis of the immune system. JAK3 has also been suggested to contribute to the pathogenesis of tumorigenesis. Recent studies identified activating JAK3 mutations in patients with various hematopoietic malignancies, including acute megakaryoblastic leukemia. Importantly, functional analyses of some of those JAK3 mutations have been shown to cause lethal hematopoietic malignancies in animal models. These observations make JAK3 an ideal therapeutic target for the treatment of various human diseases. To identify novel small molecule inhibitors of JAK3, we performed structure

SUBMITTER: Kim BH 

PROVIDER: S-EPMC2830973 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature