Mastodawn

Last paper post of the year!

Amazing Nature Chemical Biology paper by the group of Christina Woo. PCMT1 installs cyclic imides on asparagines at the C-terminus of proteins via SAM-dependent methyl ester formation, which then leads to degradation using cereblon.

https://www.nature.com/articles/s41589-025-02106-9
#Chemistry #ChemBio #TPD #TargetedProteinDegradation #Degraders

Ingo Hartung Nov 22, 2022

The drug discovery landscape is innovating at breathtaking speed. This is especially true with respect to tackling key disease drivers with a constantly evolving set of different drug modalities. Targeting #cMyc is an excellent showcase for how various innovative drug leads now start to move into clinical studies. From cell-penetrating #peptides to (ir)reversible #NCEs to co-dependency harnessing GSPT1 molecular #degraders. Great write up as always by Asher Mullard in @nature: https://www.nature.com/articles/d41573-022-00192-1

Climbing cancer’s MYC mountain

MYC, one of the most commonly dysregulated proteins in cancer, has long seemed ‘undruggable’. Can a clinical-stage cell-penetrating peptide — or preclinical small-molecule inhibitors and degraders — prove otherwise?

Chembellenie Nov 7, 2022

Some nice work from Ethan Toriki, James Papatzimas, Daniel Nomura and coauthors on bioRxiv https://www.biorxiv.org/content/10.1101/2022.11.04.512693v1

I think this is the first example in the “glue degraders” field where someone found a “degrading handle” that could be attached to multiple different inhibitors to give degradation of different proteins. A nice step forward in the rational design of molecular glue degraders!

#TPD #MedicinalChemistry #degraders