QP73

QP73 : Degrader (PROTAC) of FTO

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe QP73 is in the process of SERP review.

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Information

Degrader (PROTAC)

up to 1 uM

In Vitro Validations

Uniprot ID: Q9C0B1

Target Class: Enzyme

Target SubClass: FTO family

Potency: IC50

Potency Value: 1790 nM

Potency Assay: Inhibition of FTO demethylation via cell-free dot blot assay

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

Target aliases:

Alpha-ketoglutarate-dependent dioxygenase FTO, KIA ...

DOI Reference: 10.1016/j.apsb.2024.07.016

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): Quantitative proteomic analysis was performed on NB4 cells treated with 300 nM QP73 and found FTO was depleted after 36 h.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Relevant signaling pathways are identified but off-target effects of the FTO PROTAC degrader QP73 on other m6A modifying proteins and broader profiling outside target family are lacking. A recent paper challenges the current understanding of FB23-2 (a fluorine analog of Dac85) as a selective FTO inhibitor, demonstrating it’s primary action on hDHODH (ACS Pharmacol. Transl. Sci. 2024, 7, 12, 4096–4111). As the selectivity/off-target profile remains underexplored, the compound should be used with caution.

(last updated: 13 Feb 2025 )

SERP+ Ratings

In Cell Rating

In Model Organisms

SERP+ Comments:

The compound shows a clear time-dependent target degradation. However, selectivity profile has not been performed, so more data is needed despite proof of target engagement. The compound is well-characterised and evidence of ternary complex formation by coimmunoprecipitation assay has been provided. Related compounds and negative control are available. Upper dosing limit is not explored and the concentration at which a hook effect occurs is unknown. The compound has limited usability in vivo as the Cmax is below the DC50 and short half-life is reported (maximum is 1.25 h). Unbound fraction not reported. Nevertheless, immunoblotting demonstrated in vivo target degradation. Without target selectivity and concentration data the compound cannot be recommended as a probe and more validation data is required.

(last updated: 6 Feb 2026 )