THAL-SNS-032

Degrader (PROTAC) of CDK9, CDK10

Structure

SERP Rating

In Cells

(4 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.

Information

CDK9
CDK10

Degrader (PROTAC)

250 - 1000 nM

DOI - 10.1038/nchembio.2538

Probe Availability:

In Vitro Validations

Uniprot ID: P50750

Target Class: Kinase

Target SubClass: CMGC

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

Structure-activity relationship: no

Target aliases:

Cyclin-dependent kinase 9, TAK, CDC2L4, CDK9, CDK9 ...

DOI Reference: 10.1038/nchembio.2538

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Cell:

Within Target Family: >15-fold selectivity for Cdk9 over other CDKs (EC50 values are 62, 171 and 398 nM for Cdk2, Cdk1 and Cdk7). Outside Target Family: THAL-SNS-032 exhibited potent inhibition of proliferation across a panel of eleven different leukaemia cancer cell lines.

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 13 Mar 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

This probe is a degrader version of the inhibitor NVP-2. Both probes inhibit additional kinases in vitro, but the probe here selectively degrades CDK9 (and CDK10). Best use would be comparison of the effects due to loss of CDK9 (and CDK10) versus inhibition of these kinases. Probe has been used in the MOLT4 cell line, use of this probe in additional cell lines would need initial validation of the degradation efficiency.

(last updated: 19 Mar 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

A potential and selective PROTAC molecule to degrade cellular level of CDK9. Very fast degradation kinetics was observed. Good evidence of UPS mediated degradation using CRBN negative cell line control. DC₅₀ of this particular probe was not determined and the relevant concentration to effectively degrade CDK9 can be lower. Global degradation selectivity might be different as short time point (2h) was used in the MS experiment.

(last updated: 29 Mar 2021 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The PROTAC was well and intensively characterized and represents a very good chemical probe. However, a negative control compound for easy cellular experiment performance and validation would be appreciated. The compound shows a few off-target effects (e.g. CDK10 and GSK3A) which should be taken into regard when performing experiments.

(last updated: 17 Jun 2024 )