JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2017 Jun 20

PMID 28626520

Citations 15

Authors

Ana S Newton

Luca Deiana

David E Puleo

Jose A Cisneros

Kara J Cutrona

Joseph Schlessinger

William L Jorgensen

Affiliations

Soon will be listed here.

Abstract

A competitive fluorescence polarization (FP) assay is reported for determining binding affinities of probe molecules with the pseudokinase JAK2 JH2 allosteric site. The syntheses of the fluorescent and used in the assay are reported as well as results for 10 compounds, including JNJ7706621, NVP-BSK805, and filgotinib (GLPG0634). X-ray crystal structures of JAK2 JH2 in complex with NVP-BSK805, filgotinib, and diaminopyrimidine elucidate the binding poses.

Citing Articles

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PMID: 36678572 PMC: 9865020. DOI: 10.3390/ph16010075.

Covalent Modification of the JH2 Domain of Janus Kinase 2.

Henry S, Liosi M, Ippolito J, Menges F, Newton A, Schlessinger J ACS Med Chem Lett. 2022; 13(11):1819-1826.

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Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands.

Liosi M, Ippolito J, Henry S, Krimmer S, Newton A, Cutrona K J Med Chem. 2022; 65(12):8380-8400.

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Conversion of a False Virtual Screen Hit into Selective JAK2 JH2 Domain Binders Using Convergent Design Strategies.

Henry S, Liosi M, Ippolito J, Cutrona K, Krimmer S, Newton A ACS Med Chem Lett. 2022; 13(5):819-826.

PMID: 35586418 PMC: 9109162. DOI: 10.1021/acsmedchemlett.2c00051.

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