VZ185
Degrader (PROTAC) of BRD7, BRD9
Structure
In Cells
In Model Organisms
Information
Protein target names: BRD7, BRD9
Mechanism of action: Degrader (PROTAC)
In Vitro Validations
In Cell Validations
In Vivo Data
No in Vivo Validations
SERP ratings and comments
SERP Ratings
SERP Comments:
VZ185 is a new high-quality chemical degrader probe of BRD9 and BRD7. Its target binding and cellular effects have very convincingly been demonstrated. In vivo data have not been shown in the original paper. High affinity (low nanomolar Kd values) to Brd9 and the ternary E3 complex are shown by orthogonal biophysical assays. A fast, complete, and lasting degradation of Brd7 and Brd9 was seen in cells and degradation was confirmed in several cell types. The mechanism of action was validated by carefully designed control experiments, and selective degradation of BRD7/9 was demonstrated by proteomics. VZ185 showed high water solubility and stability in blood plasma and microsomes. Membrane permeability (PAMPA) is low; thus, the high cell activity is perhaps due to the catalytic mechanism of PROTACs. Of note, in some cells a high concentration (1 µM) of VZ185 induced less degradation than a low concentration (10-100 µM), which is suggested to be due to the so-called hook effect.
(last updated: 26 Feb 2021 )
SERP Ratings
SERP Comments:
VZ185 together with its published inactive control is an excellent degrader of the bromodomain proteins BRD7 and BRD9. MS based experiments showed that this PROTAC is highly selective and potent. Experimental validation is sound the PROTAC is comprehensively profiled. The PROTAC has not be optimized for in vivo use.
(last updated: 12 Mar 2021 )
SERP Ratings
SERP Comments:
(last updated: 12 Mar 2021 )