Molecular Docking Analysis of Novel JAK-2 Inhibitors for Therapy of Myeloproliferative Neoplasms

Abstract

Background and Objectives: Januskinase-2 (JAK2) is an intracellular, non-receptor tyrosine kinase belonging to the family of Janus kinase that also includes JAK1, JAK3 and TYK2.The recent discovery of JAK2's acquired point mutation V617F led to greater understanding its oncogenic role in Myeloproliferative tumors (MPN’S). At 617 position phenylalanine amino acid was replaced by valine due to mutation. Therefore, aiming abnormal JAK-2 to prevent its essential activation will be an optimistic alterative option in the treatment of Myeloproliferative tumors.

Methods: In this current study, using computational methods we have designed 114 novel Quinazoline JAK2 –inhibitors and evaluated them for interaction with the enzyme JAK2 through insilico analysis like prediction of pharmacokinetics & Molecular docking studies.

Results: Among the designed 114 novel Quinazoline JAK2 – inhibitors 98 compounds were shown good activity with better dock scores and good ADMET properties with no Lipinski rule violation.

Conclusion: Our present study concludes that the designed novel Quinazoline JAK2 –inhibitors are having potent anticancer activity.