Identification of a Novel Inhibitor of JAK2 Tyrosine Kinase by Structure-based Virtual Screening

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2009 May 19

PMID 19447617

Citations 19

Authors

Robert Kiss

Timea Polgar

Annet Kirabo

Jacqueline Sayyah

Nicholas C Figueroa

Alan F List

Lubomir Sokol

Kenneth S Zuckerman

Meghanath Gali

Kirpal S Bisht

Peter P Sayeski

Gyorgy M Keseru

Affiliations

Soon will be listed here.

Abstract

Janus kinase 2 (JAK2) plays a crucial role in the pathomechanism of myeloproliferative disorders and hematologic malignancies. A somatic mutation of JAK2 (Val617Phe) was previously shown to occur in 98% of patients with polycythemia vera and 50% of patients with essential thrombocythemia and primary myelofibrosis. Thus, effective JAK2 kinase inhibitors may be of significant therapeutic importance. Here, we applied a structure-based virtual screen to identify novel JAK2 inhibitors. One JAK2 inhibitor in particular, G6, demonstrated remarkable potency as well as specificity, which makes it as a potential lead candidate against diseases related to elevated JAK2 tyrosine kinase activity.

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