dWIZ1

dWIZ1 : Molecular Glue of WIZ

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe dWIZ1 is in the process of SERP review.

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Information

Molecular Glue

up to 10 µM
Reviewer recommended concentration: 1 µM

In Vitro Validations

Uniprot ID: O95785

Target Class: Transcription factor

Target SubClass: Zinc Finger

Potency: Kd

Potency Value: 3500 nM

Potency Assay: SPR binding of WIZ ZF7 to the DDB1:CRBN:dWIZ-1 complex

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

Target aliases:

Protein Wiz, ZNF803, WIZ, WIZ_HUMAN, Zinc finger p ...

DOI Reference: 10.1126/science.adk6129

Uniprot ID: O95785

Target Class: Transcription factor

Target SubClass: Zinc Finger

Potency: IC50

Potency Value: 170 nM

Potency Assay: Cereblon association

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

Target aliases:

Protein Wiz, ZNF803, WIZ, WIZ_HUMAN, Zinc finger p ...

DOI Reference: 10.1126/science.adk6129

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Primary human erythroblasts were treated with 10 μM compound C or dimethyl sulfoxide (DMSO) control for 6 hours. From 8960 quantified proteins, the most significantly down-regulated protein was the WIZ TF. Compound C proved selective for WIZ, with no additional proteins depleted more than twofold. Compound C did not affect the abundance of known HbF regulators and was also selective over known lenalidomide targets IKZF1 and CK1α.

Potency assay, off target (cells): IKZF1 HiBiT degradation (DC50 / Dmax) >50000 nM / 0 % GSPT1 HiBiT degradation (DC50 / Dmax) >50000 nM / 0 %

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

dWIZ1 is a very well characterized probe for the selective degradation of the transcription factor WIZ for in vitro assays (including primary erythroblasts) up to 10 uM (higher concentration should be avoided due to unknown toxicity). Due to higher target selectivity over dWIZ2, dWIZ1 should be preferred for in vitro assays. However, PK properties of dWIZ1 are not optimal for use with in vivo models (oral administration), for which dWIZ2 has been better characterized being at this time the best in class probe for in vivo degradation of WIZ (both mouse and monkey models).

(last updated: 15 Aug 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

I recommend 1 micromolar as the single-point dosage. (I would note that proteomics was done at 10 uM and WIZ is reduced the most and with the highest significance.) The authors do not appear to indicate the concentration at which the Hook effect comes into play, nor time to reach Dmax.The paper suggests that dWIZ-2 has more drug-like properties.

(last updated: 25 Nov 2024 )