DKY709

DKY709 : Molecular glue degrader of IKZF2

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe DKY709 is in the process of SERP review.

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Information

IKZF2

Molecular glue

up to 1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: Q9UKS7

Target Class: Transcription factor

Target SubClass: Zinc Finger

Potency: IC50

Potency Value: 130 nM

Potency Assay: Biochemical CBRN binding assay

PDB ID for probe-target interaction (3D structure): 8DEY

Target aliases:

Zinc finger protein Helios, ZNFN1A2, HELIOS, IKZF2 ...

DOI Reference: 10.1016/j.chembiol.2023.02.005

Uniprot ID: Q9UKS7

Target Class: Transcription factor

Target SubClass: Zinc Finger

Potency: Kd

Potency Value: 190 nM

Potency Assay: SPR of the trimeric complex with ZF2 and 3

PDB ID for probe-target interaction (3D structure): 8DEY

Target aliases:

Zinc finger protein Helios, ZNFN1A2, HELIOS, IKZF2 ...

DOI Reference: 10.1016/j.chembiol.2023.02.005

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : DC50 13 nM (88% Dmax)

Potency assay (off target): Selective against IKZF1, GSPT1 possible SALL4 off-target was discarded after cellular assay.

Potency assay, off target (cells): Quantitative proteomics profiling of Jurkat cells treated for 16 h with 2.5 μM DKY709 or DMSO display DKY709 to be selective against IZKF3 DC50 > 50uM (IZKF4 13 nM DC50 but Dmax is only 21%)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

DKY709 is a very well-characterized molecular glue degrader of IKZF2 and an excellent probe. Similar in structure to pomalidomide, DKY709 was successfully designed to not degrade other neosubstrates of pomalidomide like IKZF1, IKZF3, and GSPT1. Selectivity is demonstrated with a quantitative proteomics study and rationalized with X-ray crystallography. Appropriate PK studies in multiple species enable accurate in vivo dosing. Of note: DKY709 partially degrades IKZF4 and quite effectively degrades SALL4; therefore, users should take care to confirm whether these proteins are expressed in their experimental system or control whether they play a role in any identified phenotypes.

(last updated: 8 Feb 2024 )