ML323
Allosteric inhibitor of USP1, WDR48
Structure
In Cells
In Model Organisms
Information
Protein target names: USP1, WDR48
Mechanism of action: Allosteric inhibitor
In Vitro Validations
DOI Reference: 10.1038/nchembio.1455
In Cell Validations
In Vivo Data
No in Vivo Validations
Reagent authentication certificate:
SERP ratings and comments
SERP Ratings
Comments:
ML323 is a selective USP1/UAF1 inhibitor that has been shown to have good Caco-2 permeability and to be efficacious in cellular assays at ≥5 µM. A compound in the same series (compound 77 in J. Med. Chem., 2014, 8099-8110) can be used as an inactive control. ML323 was found to have rapid clearance and has not been proposed for use in vivo.
(last updated: 15 Jan 2017 )
SERP Ratings
Comments:
ML323 is an allosteric, selective inhibitor of the USP1/UAF1 complex (also called USP1/WDR48). Note that ML323 is much less effective in inhibiting USP1 alone in biochemical assays. The full implications or relevance of this differential activity in cells has not been explored.
(last updated: 16 Jan 2017 )
SERP Ratings
Comments:
ML-323 is a unique, cell-permeable and highly selective inhibitor of the USP1/UAF1 complex. A notable discordance between biochemical and cellular potency for ML-323 is observed, and should be further examined. Furthermore, a more direct, biophysical assessment of intracellular target engagement would be valuable to explore the mechanism of the observed IC50 offset.
(last updated: 22 Jan 2017 )