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G-5555 | ATP competitive of PAK1, PAK2, PAK3
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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:3.7 nM
  • IC50:69 nM
PAK2
  • Ki:3.7 nM
  • IC50:69 nM
PAK3
  • Ki:3.7 nM
  • IC50:69 nM
ATP competitive
70 - 250 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
IC50s: SIK2: 9 nM KHS1: 10 nM MST4: 20 nM MST3: 43 nM YSK1: 34 nM LCK: 52 nM
Selectivity Assessment Description:
5HT1B: 84% inhibition at 10 uM 5HT2B: 92% at 10 uM

Potency
Cellular
In Vitro

PAK1

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.5b00398

PAK2

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.5b00398

PAK3

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.5b00398

In Vivo Validations

Mouse
Dose: 2 mg/kg
Route of delivery: Intravenous
Plasma half life: 0.886 h
Systemic clearance: 24.2 mL/min/kg
Area Under the Curve:: 3.21 uM*h
Volume of Distribution at Steady-State: 1.55 L/Kg

DOI Reference: 10.1021/acsmedchemlett.5b00398

Dose: 25 mg/Kg
Route of delivery: Oral
Cmax: 9.63 uM
Tmax: 0.5 h
Area Under the Curve:: 29.9 uM*h
Bioavailability: 79.5%

DOI Reference: 10.1021/acsmedchemlett.5b00398

Negative Control Compounds

(R)-6-(2-Chloro-4-(4-methyl-2-oxopyridin-1(2H)-yl)phenyl)- 2-(methylamino)-8-(morpholin-2-ylmethyl)pyrido[2,3-d]- pyrimidin-7(8H)-one

Orthogonal Probes def

FRAX1036
NVS-PAK-1

Chemical Information

Molecular Formula C25H25ClN6O3
SMILEs CNc1ncc2cc(-c3ccc(-c4cccc(C)n4)cc3Cl)c(=O)n(C[C@H]3OC[C@H](N)CO3)c2n1
InChI InChI=1S/C25H25ClN6O3/c1-14-4-3-5-21(30-14)15-6-7-18(20(26)9-15)19-8-16-10-29-25(28-2)31-23(16)32(24(19)33)11-22-34-12-17(27)13-35-22/h3-10,17,22H,11-13,27H2,1-2H3,(H,28,29,31)/t17-,22-
Molecular weight 492.17 Da
AlogP 3.22422
HBond acceptors 9
HBond donors 3
Atoms 60

References

Publications

Cross References

ChEMBL BindingDB PDB canSAR

Vendors

Note: This is not an exhaustive list and does not indicate endorsement by the Portal.

Expert Reviews

by SERP
(on 7 Jan 2017)
Cellular Use Rating
In Model Organisms
Starting with an advanced inhibitor, the authors optimized a PAK1-inhibitory compound for potency and selectivity. Based on analysis of their SAR tables, the authors did a good job balancing...
by SERP
(on 9 Jan 2017)
Cellular Use Rating
In Model Organisms
This is a potent inhibitor of Group I PAK enzymes (PAK1, 2 and 3; PAK1 Ki = 4 nM) that has been screened versus 235 kinases at 100 nM, with biochemical inhibition of 5 kinases (IC50 <50 nM) observed....
by SERP
(on 12 Jun 2017)
Cellular Use Rating
In Model Organisms
G-5555 is one of a number of quality compounds now available for the study of the function of group 1 PAKs, and its use in cells is recommended, especially if used alongside other chemotypes such as...
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