molecules of the month


oral, brain-penetrant LRRK2 kinase inhibitor

recapitulated LRRK2 lung tox. in model

discovery details manuscript in preparation

J. Pharmacol. Exp. Ther., Jan. 28, 2021

Merck & Co., Inc., Boston, MA

Chemical structure of molecule MLi-2 inhibitor
1 min read

The Merck LRRK2 inhibitor, MLi-2, is an orally available tool compound that is structurally distinct from the LRRK2 inhibitor GNE-7915. LRRK2 had been a highly attractive target for treating Parkinson’s disease, but pulmonary toxicity observed with LRRK2 inhibition in non-human primates (NHP) cast a shadow on the utility of LRRK2 inhibitors. Since NHP studies are cost and resource-intensive, it was difficult to study the toxicity in depth. The Merck team was able to recapitulate the pulmonary toxicity in rodents with MLi-2, and found that the lung effects were due to chronic LRRK2 inhibition and were mild and readily reversible. This study provides a higher-throughput method to assess new LRRK2 inhibitor scaffolds and more broadly understand on-target effects of LRRK2 inhibition.

request a trial

You don’t have time to read everything, but you can’t afford to fall behind.

Drug Hunter Premium is drug discovery, distilled, so you can quickly catch up and make informed decisions based on industry examples.

Get ahead now by requesting a trial.

already a member? log in: