Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2^V617F against myeloproliferative neoplasms.

ABSTRACT:

Background

The JAK2-STAT signaling pathway plays a critical role in myeloproliferative neoplasms (MPN). An activating mutation in JAK2 (V617F) is present in ~ 95% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis cases. This study aims to explore the selective JAK2^V617F inhibitor, evaluate the efficacy and possible mechanism of ZT55 on MPN.

Methods

HTRF assays were conducted to evaluate the selective inhibition of ZT55 for JAKs. Cell apoptosis, proliferation, and cycle arrest assays were performed to examine the effect of ZT55 on HEL cell line with JAK2^V617F mutation in vitro. Western analysis was used to monitor the expression and activity of proteins on JAK2/STAT pathway. A mice xenograft model was established to evaluate the

SUBMITTER: Hu M 

PROVIDER: S-EPMC6360668 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature