MEN1 mutations mediate clinical resistance to menin inhibition

Perner F, Stein EM, Wenge DV, Singh S, Kim J, Apazidis A, Rahnamoun H, Anand D, Marinaccio C, Hatton C, Wen Y, Stone RM, Schaller D, Mowla S, Xiao W, Gamlen HA, Stonestrom AJ, Persaud S, Ener E, Cutler JA, Doench JG, McGeehan GM, Volkamer A, Chodera JD, Nowak RP, Fischer ES, Levine RL, Armstrong SA, Cai SF
Nature 615:913, 2023 [DOI]

We describe how mutants that confer therapeutic resistance to menin inhibition impact small molecule binding but not interactions with the natural ligand MLL1.

A white-knuckle ride of open COVID drug discovery

Frank von Delft, Mark Calmiano, John Chodera, Ed Griffen, Alpha Lee, Nir London, Tatiana Matviuk, Ben Perry, Matt Robinson, and Annette von Delft.
Nature 594:330, 2021.
[DOI] [PDF]

The COVID Moonshot is an open science effort to discover a direct-acting SARS-CoV-2 oral antiviral. Here, we share lessons from this effort, including the missed opportunity to develop a phase 2 ready drug more than a decade ago that could have halted the COVID-19 pandemic in its tracks.