Identification of 8 ‐Hydroxyquinoline Derivatives Active Against Somatic V658F Mutant JAK1‐Dependent Cells

We present the results of an extensive virtual screening campaign based on a multi‐step screening protocol involving ligand docking. The screening yielded five new, experimentally validated inhibitors of JAK1 with 8‐hydroxyquinoline as a novel hinge‐binding scaffold. The compounds did not only display favorable potencies in a JAK1V658F‐driven cell‐based assay but were also shown to be non‐cytotoxic on rat liver cells.

An extensive virtual screening campaign was carried out, resulting in multiple novel JAK1 inhibitors with the 8‐hydroxyquinoline scaffold as the hinge‐binding motif. The compounds have been shown to inhibit JAK1V658F‐driven cell growth and to be non‐cytotoxic to rat liver cells. Hence, they represent valuable starting points for JAK1V658F‐involving disease conditions, including acute lymphoblastic leukemia.

Source: Archiv der Pharmazie - November 9, 2016 Category: Drugs & Pharmacology Authors: R óbert Kiss, Dávid Bajusz, Rebekah Baskin, Katalin Tóth, Katalin Monostory, Peter P. Sayeski, György M. Keserű Tags: Full Paper Source Type: research