Identification of Malate Dehydrogenase 2 as a Target Protein of the HIF-1 Inhibitor LW6 using Chemical Probes

Tracking the target: To identify a protein that binds directly to the HIF‐1α inhibitor LW6, a series of new chemical probes were synthesized with a clickable tag and/or a photoactivatable moiety. LW6 was found to be localized to the mitochondria (see picture) and MDH2 was identified as a target protein of LW6. These results indicate that the HIF‐1α inhibitory activity of LW6 is a consequence of MDH2 suppression.