UNC6852

UNC6852 : Degrader (PROTAC) of EED and PRC complex

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe UNC6852 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

EED
EZH2
SUZ12

Degrader (PROTAC)

up to 10 uM
Reviewer recommended concentration: 10 µM to reliably degrade the target

Probe Availability:

In Vitro Validations

Uniprot ID: O75530

Target Class: Epigenetic

Target SubClass: --

Potency: IC50

Potency Value: 247 nM

Potency Assay: IC50 of EED was tested by the TR-FRET assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Polycomb protein EED, EED, EED_HUMAN, WAIT-1, hEED ...

DOI Reference: 10.1016/j.chembiol.2019.11.006

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Global proteomics experiments using tandem mass tag quantification comparing HeLa cells treated with UN6852 (10 μM, 24 h).

Probe Selectivity in Vitro:

EED and EZH2 were selectively degraded by UNC6852 within the proteome. Modest SUZ12 degradation (21%) was observed. EZH1 was not identified in the proteomics analysis, presumably due to low levels of EZH1 expression.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Degradation of target proteins is dependent on cellular VHL expression. The activity may be lower / recommended cellular concentration higher in cells with low VHL expression (e.g., platelets). Degradation of SUZ12 is incomplete / modest relative to EED and EZH2. Active on both wild type and mutant EZH2. Anti-proliferative effects are evident in cells (e.g., DLBCL cell lines) bearing gain of function EZH2 mutations. The capacity of UNC6852 to degrade EZH1 has not been determined. This probe has not yet been evaluated in vivo.

(last updated: 16 Mar 2022 )

SERP Ratings

In Cell Rating

(last updated: 10 Apr 2022 )