PT-65

PT-65 : Degrader (PROTAC) of GSK3A, GSK3B

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe PT-65 is in the process of SERP review.

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Information

GSK3A
GSK3B

Degrader (PROTAC)

up to 500 nM

Probe Availability:

Glixx Laboratories Inc

In Vitro Validations

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): The selectivity of PT-65 was evaluated by the global proteome analysis using tandem mass tag (TMT)-based quantitative proteomics technology. Cells were treated with PT-65 for 4 h and, out of the 7499 identified proteins, only seven proteins, GSK3β, GSK3α, PDE4A, AF17, S41A3 and PLD6 were significantly downregulated.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The proteomics for this compound was done in singlicate (and the raw data is not available), so there is no P-values/fold change information available. I, therefore, think it will not be possible to adequately evaluate the selectivity of this compound without this data.

(last updated: 18 May 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

This molecule can potently degrade with GSK3a and GSK3b with a relatively rapid degradation profile at 1uM in SHSY5Y cells. Adequate controls are provided to demonstrate proteasomal dependence and competition with a CRBN E3 ligase binder. However, no negative control is presented and most importantly the data provided is not sufficient to inform on proteome-wide selectivity. In that regard, it is not possible to assess the quality of this molecule as a selective cellular probe for the dual degradation of GSK3a and GSK3b.

(last updated: 19 May 2023 )