BSJ-4-116

BSJ-4-116 : Degrader (PROTAC) of CDK12

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

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Information

CDK12 (Mutant:WT, C1039F)

Degrader (PROTAC)

~~up to 400 nM~~
Reviewer recommended concentration: 50 nM; 150 nM not exceeding 400 nM.

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9NYV4

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 6 nM

Potency Assay: radioactive CDK12/Cyclin K in vitro kinase assay

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

Target aliases:

Cyclin-dependent kinase 12, KIAA0904, CRKRS, CRK7, ...

DOI Reference: 10.1038/s41589-021-00765-y

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Kinomescan S(10)=0.017, profiled at a concentration of 1 μM against a panel of 468 human kinases

Potency assay, off target (cells): The selectivity for degradation was assessed by proteome-wide profiling using Jurkat cells that were treated with 50 nM BSJ-4-116 for 8 h, then subjected to a multiplexed mass spectrometry (MS)-based proteomic analysis. These experiments detected CDK12 as the only kinase that was significantly degraded (by fourfold)

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 9 Jan 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

BSJ-4-116 and its negative control compound BSJ-4-116-NC represent a well characterized pair of substances for use in interrogating selective CDK12 degradation, at least in the cell lines that were used in the original manuscript. BSJ-4-116 may be less valuable as a selective CDK12 inhibitor, due to its "only" having a good but not excellent kinase inhibitor selectivity profile, so users should take this compound when their interest is in CDK12 degradation studies. One thing to keep in mind is that the proteomics experiment, which is the basis for claiming degrader selectivity, was conducted at 50 nM. If higher concentrations (recommended use is up to 400 nM) are used, other proteins may also be more effectively degraded.

(last updated: 30 Jan 2023 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

There is a difference between the proteomics profile and western blotting as the former shows degradation of CDK13 and the latter doesn't. Therefore, CDK13 may be an off-target.

(last updated: 31 Oct 2024 )