Chemical inhibition of PIN auxin transporters by the anti-inflammatory drug Naproxen

The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we uncover that Naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN transporters in plants. Physiological experiments indicate that exogenous Naproxen treatment affects pleiotropic auxin-regulated developmental processes. Further cellular and biochemical evidence supports that Naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analysis confirms that Naproxen binds directly to PIN1 protein, via the same binding cavity as the IAA substrate. Thus, by combining cellular, biochemical, and structural approaches, this study well establishes that Naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of the compound may advance our understanding on the molecular mechanisms of PIN-mediated auxin transport, and expand our toolkit in auxin biology and agriculture. ### Competing Interest Statement The authors have declared no competing interest.