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CPS-021 | CPS-021 : Degrader (PROTAC) of PAK4
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
PAK4
  • IC50:382.7 ± 7.2 nM
  • DC50:500 nM
  • DC50:50 nM
  • Dmax:72%
Degrader (PROTAC)
up to 1 µM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
CPS-021 effectively decreased the phosphorylation of PAK4 in A549 and MDA-MB-231 cell lines. CPS-021 ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
CPS-021-Incubated A549 cells were checked via Proteomic analysis to identify up- and down- regulated ...

Potency
Cellular
In Vitro

PAK4

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/acs.jmedchem.5c00197

In Vivo Validations

Mouse
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 3.32 ± 1.24 h
Systemic clearance: 52.12 ± 13.21 mL/min/Kg
Cmax: 459.90 ± 58.36 ng/mL
Tmax: 0.0833 h
Area Under the Curve:: 332.62 ± 76.62 ng·h/mL)
Volume of Distribution at Steady-State: 8.59 ± 3.08 L/Kg

DOI Reference: 10.1021/acs.jmedchem.5c00197

Dose: 2 mg/Kg
Route of delivery: Oral
Plasma half life: 1.36 ± 0.26 h
Cmax: 343.11 ± 51.12 ng/mL
Tmax: 2.00 h
Area Under the Curve:: 1191.40 ± 71.71 ng·h/mL
Bioavailability: 183.47 ± 11.60%

DOI Reference: 10.1021/acs.jmedchem.5c00197

Negative Control Compounds

canSAR7437555
Notes: The methyl PROTAC PS21M attenuated its interaction with Cereblon ligase and thus limited the formation of the PAK4-PROTAC-Cereblon ternary complex and subsequently PAK4 degradation.

Chemical Information

Molecular Formula C52H63N11O7
SMILEs Nc1nccc(-n2cc(C(=O)N3CCN(CCCCCCCC(=O)N4CCN(CCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)c3ccc(C#CC4(O)CCCCC4)cc32)n1
InChI InChI=1S/C52H63N11O7/c53-51-55-22-18-43(56-51)62-35-39(37-14-13-36(34-42(37)62)17-21-52(70)19-6-4-7-20-52)48(67)61-32-28-58(29-33-61)24-8-3-1-2-5-12-45(65)60-30-26-59(27-31-60)25-23-54-40-11-9-10-38-46(40)50(69)63(49(38)68)41-15-16-44(64)57-47(41)66/h9-11,13-14,18,22,34-35,41,54,70H,1-8,12,15-16,19-20,23-33H2,(H2,53,55,56)(H,57,64,66)
Molecular weight 953.49 Da
AlogP 3.8053000000000043
HBond acceptors 18
HBond donors 5
Atoms 133

References

Publications

Cross References

Expert Reviews

by SERP
(on 12 Aug 2025 )
Cellular Use Rating
In Model Organisms
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...
by SERP
(on 17 Aug 2025 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
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