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PF-3758309 | PF-3758309 : ATP competitive inhibitor of PAK1, PAK4, PAK5, PAK6
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (4 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
PAK1
  • Ki:13.7 nM
  • IC50:1.3 nM
PAK4
  • Ki:PAK4 18.7 nM
  • Kd:2.7 nM
  • Kd:4.5 nM
  • IC50:1.3 nM
PAK5
  • Ki:18.1 nM
  • IC50:1.3 nM
PAK6
  • Ki:17.1 nM
  • IC50:1.3 nM
ATP competitive
0.1 - 300 nM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
In kinase assays, PF-3758309 inhibited multiple off-target kinases of 146 tested: SRC, FYN, YES, AMP ...

Potency
Cellular
In Vitro

PAK1

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1073/pnas.0911863107

PAK4

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1073/pnas.0911863107

PAK5

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1073/pnas.0911863107

PAK6

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1073/pnas.0911863107

In Vivo Validations

Mouse
Dose: 7.5-30 mg/kg
Route of delivery: Oral
Organ of interest (O): xenograft
Target engagement assay: Indirect: inhibition of protein substrate phosphorylation in xenograft tissue

DOI Reference: 10.1073/pnas.0911863107

Orthogonal Probes def

GNE-2861

Chemical Information

Molecular Formula C25H30N8OS
SMILEs Cc1nc(Nc2[nH]nc3c2CN(C(=O)N[C@H](CN(C)C)c2ccccc2)C3(C)C)c2sccc2n1
InChI InChI=1S/C25H30N8OS/c1-15-26-18-11-12-35-20(18)23(27-15)29-22-17-13-33(25(2,3)21(17)30-31-22)24(34)28-19(14-32(4)5)16-9-7-6-8-10-16/h6-12,19H,13-14H2,1-5H3,(H,28,34)(H2,26,27,29,30,31)/t19-/m1/s1
Molecular weight 490.23 Da
AlogP 0.0
HBond acceptors 9
HBond donors 3
Atoms 65

References

Publications

Cross References

canSARChEMBLBindingDBBindingDB

Vendors

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Expert Reviews

by SERP
(on 1 Jul 2016 )
Cellular Use Rating
In Model Organisms
This probe meets minimal criteria for use in cellular and in vivo assays. It has additional biochemical activity in the PAK subfamily: PAK2: IC50 = 190 nM, PAK3: IC50 = 99 nM (PMID 20439741). No antiproliferative...
by SERP
(on 19 Oct 2016 )
Cellular Use Rating
In Model Organisms
PF3758309 is reportedly potent against PAK4 (3-18 nM, depending on the assay format). Using a peptide phosphorylation assay, PF3758309 does not appear to be selective for PAK4 over PAK1, 5, and 6; it...
by SERP
(on 4 Nov 2016 )
Cellular Use Rating
In Model Organisms
PF-3758309 is reported as a potent, ATP-competitive inhibitor of PAK4 with additional activity against PAK1, PAK5 and PAK6, and, to a slightly lesser degree PAK3 and PAK2 (range of affinities PAK4 IC50=3...
by SERP
(on 1 Apr 2021 )
Cellular Use Rating
In Model Organisms
I would not recommend PF3758309 as a specific probe. While earlier data already have uncovered significant off-target activities, including potent CDK7 inhibition (J Med Chem 58, 111–129 (2015)), a...
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. Read more about our evaluation criteria