CPS-021

CPS-021 : Degrader (PROTAC) of PAK4

Structure

SERP Rating

In Cells

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In Model Organisms

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Probe CPS-021 is in the process of SERP review.

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Information

PAK4

Degrader (PROTAC)

up to 1 µM

In Vitro Validations

Uniprot ID: O96013

Target Class: Kinase

Target SubClass: STE

Potency: IC50

Potency Value: 382.7 ± 7.2 nM

Potency Assay: HTRF Kinase Binding Assay

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

Target aliases:

Serine/threonine-protein kinase PAK 4, KIAA1142, P ...

DOI Reference: 10.1021/acs.jmedchem.5c00197

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): CPS-021 effectively decreased the phosphorylation of PAK4 in A549 and MDA-MB-231 cell lines. CPS-021 performed excellent selectivity against PAK5, as only the relative abundance of pPAK4 rather than pPAK5 decreased in both cell lines.

Potency assay, off target (cells): CPS-021-Incubated A549 cells were checked via Proteomic analysis to identify up- and down- regulated proteins (after 14 h coincubation of 5 μM CPS-021): 201 differential proteins were identified. Among them, 57 proteins were significantly upregulated, and 144 proteins were downregulated.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Several proteins are down-regulated in the proteomics analysis. It is therefore unclear how selective the PROTAC is. Running proteomics at an earlier timepoint and/or lower compound concentration may provide improved clarity on this. From the current data, it appears non-selective. Due to the questions around in vitro selectivity, I would expect more data to be obtained before this is used as a chemical probe in vivo. There is also no in-vivo efficacy data or modelling shown for doses <5mg/k in the paper and thus it's unclear whether the doses of 1 and 2mg/kg would have the appropriate pharmacological effect.

(last updated: 12 Aug 2025 )