fbpx

molecules of the month

NJH-2-057

covalent allosteric OTUB1-recruiting DUBTAC

induced deubiq./stabilization of _F508-CFTR

from gel-based screen of 702 covalent ligands

bioRxiv, Apr. 30, 2021

UC Berkeley / Novartis (NIBR)

NJH-2-057
1 min read

The UC Berkeley and Novartis deubiquitinating enzyme-recruiting chimera (DUBTAC), NJH-2-057, has a warhead that covalently targets a non-catalytic allosteric cysteine on the deubiquitinase (DUB) OTUB1. The CFTR-binding moiety recruits OTUB1 to the mutant ion channel, ΔF508-CFTR, stabilizing the protein by preventing its polyubiquitination and degradation. This work provides an interesting proof of concept for targeted protein stabilization rather than degradation via DUB recruitment. We recently highlighted a number of new chimeric modalities, including ribonuclease recruiting chimeras (RIBOTACs), phosphatase recruiting chimeras (PhoRCs), LYTACs, and AUTACs, and this introduction of a deubiquitinating enzyme-recruiting chimera will add another valuable concept to the pharmacological toolbox. Note: This molecule was originally highlighted from an RXiV entry: https://doi.org/10.1101/2021.04.30.441959v1 - the link has been updated to reflect a new publication.


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: