Keith HornbergerNov 14, 2022

Apparently an #introduction is in order over here, so here’s mine.

I’m a medicinal chemist with 20+ years in pharma. Now at #Arvinas working on protein degradation #TPD. I post on TPD, med chem “wisdom”, industry careers, and pharmacology/PK tweetorials. Before Arvinas, I worked in med chem at GSK, OSI/Astellas, and Boehringer Ingelheim. I have a PhD in synthetic organic chemistry from #Columbia. In my spare time, I wrangle 3 kids, drink and brew beer, and go hiking all over Connecticut.

Keith HornbergerNov 11, 2022
Hot off the press: in vivo active SMARCA2 degraders, courtesy of a joint effort between my #Arvinas colleagues and collaborators at #Genentech.
https://www.nature.com/articles/s41467-022-34562-5
Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers - Nature Communications

SMARCA2 has been identified as a synthetic lethal target in SMARCA4 mutated tumors, however, homology between the two has hindered the development of selective SMARCA2 inhibitors. Here, the authors synthesize a proteolysis targeting chimera (PROTAC) capable of SMARCA2 specific degradation and demonstrate its utility in the treatment of SMARCA4 mutated tumors.

Nature