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Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening.

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.

SUBMITTER: Kiss R

PROVIDER: S-EPMC2812898 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening.

Kiss Róbert R Polgár Tímea T Kirabo Annet A Sayyah Jacqueline J Figueroa Nicholas C NC List Alan F AF Sokol Lubomir L Zuckerman Kenneth S KS Gali Meghanath M Bisht Kirpal S KS Sayeski Peter P PP Keseru György M GM

Bioorganic & medicinal chemistry letters 20090505 13

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 inhib ...[more]

PMID: 19447617

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