CPS2

CPS2 : Degrader (PROTAC) of CDK2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe CPS2 is in the process of SERP review.

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Information

CDK2

Degrader (PROTAC)

up to 1 uM

In Vitro Validations

Uniprot ID: P24941

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 24 nM

Potency Assay: Caliper Mobility shift assay

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

Target aliases:

Cyclin-dependent kinase 2, CDKN2, CDK2, CDK2_HUMAN ...

DOI Reference: 10.1038/s41589-021-00742-5

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Kinome scan for 1 μM CPS2 highlighted unwanted interactions with AURKA and KDR. Cell-free binding-affinity experiment were conducted to determine the half-maximum inhibitory concentration (IC50) and to explore the possibility of CPS2 acting as an inhibitor. CPS2 maintained a 24 nM IC50 against CDK2, while the IC50 of other possible off-targets decreased to submicromolar levels

Potency assay, off target (cells): Proteomics analysis was performed in NB4 cells treated with 250-nM CPS2 for 6 h confirming CDK2 was the main target with a potential AURKA off-target.

Potency assay, off target (cells): Selectivity within target family: CPS2 induced only CDK2 degradation and did not directly perturb the other CDK proteins (such as CDK1, 4, 5, 6, 7, 8 and 9) under subnanomolar concentration conditions

Probe Selectivity in Cell:

Western blot

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Users are advised to re-assess the DC50 (both for CDK2 and for AURKA) of the compounds since the published data are conflicting. The Recommended In Cell Concentration should be in the range of 250 to 500 nM, according to the proteomics study. It's noteworthy that the degrader is less toxic than the inhibitor.

(last updated: 20 Feb 2025 )

SERP Ratings

In Cell Rating

SERP Comments:

CPS2 is a valuable tool compound for investigating CDK2 biology and the therapeutic potential of CDK2 degradation. At a concentration of 250 nM and following 6 hours of treatment of NB4 cells, CPS2 induces significant degradation of both CDK2 and AURKA—an important consideration for potential users. The original publication also includes kinome-wide profiling at 1 μM concentration. Given its potent degradation activity, the compound’s inhibitory effects are likely negligible at concentrations below 250 nM. CPS2 exhibits DC₅₀ values in the double-digit nanomolar range across seven different cell lines. Its mechanism of action has been thoroughly validated. A structurally related negative control compound, which is incapable of binding CRBN, is also described in the original study. Overall, CPS2 can be considered one of the best chemical probes currently available (as of April 2025) for studying CDK2.

(last updated: 16 Apr 2025 )