molecules of the month


orally active covalent menin-MLL PPI inhibitor

efficacy in xenograft (300 mpk PO QD)

warhead addition to rev. inh. and opt.

Journal of Medicinal Chemistry

University of Michigan, Ann Arbor, US

1 min read

9. The University of Michigan menin-MLL inhibitor, M-1121, is a covalent protein-protein interaction inhibitor that is orally active and achieves complete tumor regression in a xenograft model (300 mpk PO QD). MLL gene fusions are drivers of leukemias via interaction with menin, and small molecule menin-MLL inhibitors have shown preliminary activity in trials (KO-539, NCT04067336 and SNDX-5613, NCT4065399). M-1121 has a non-covalent scaffold with features reminiscent of prior reversible inhibitors (e.g. MI-503 and VTP-50469) with an acrylamide warhead targeting MLL's Cys329. Though it is given at a high dose in mouse, the in vivo activity of the molecule is impressive given its large size, acrylamide warhead, the presence of two basic nitrogens, 7 rings, and several hydrogen-bond acceptor and donor…

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: