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NVS-PAK1-1 | NVS-PAK1-1 : Allosteric inhibitor of PAK1
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
  • IC50:5 nM
  • Kd:7 nM
  • IC50:200 nM
Allosteric
400 nM - 2 uM

Selectivity

In Vitro Selectivity Assessment

Potency: KD - PAK2=400 nM

Potency Assay Off-Target:
Selectivity for PAK1 > PAK2 = 57-fold. It demonstrated a selectivity score (S10-score) of 0.003 whe ...
Selectivity Assessment Description:
No significant inhibition of CYP450s (13.2 μM for 3A4 the midazolam site, >20 μM for 2D6 and 16.7 μM ...

Potency
Cellular
In Vitro

PAK1

Mode of Action: Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.5b00102

In Vivo Validations

Poor stability in rat liver microsomes limit its application in vivo
Dose:

Reference: --

Orthogonal Probes def

G-5555

Chemical Information

Molecular Formula C23H25ClF3N5O
SMILEs CC(C)NC(=O)N1CC[C@H](NC2=Nc3cc(F)ccc3N(CC(F)F)c3ccc(Cl)cc32)C1
InChI InChI=1S/C23H25ClF3N5O/c1-13(2)28-23(33)31-8-7-16(11-31)29-22-17-9-14(24)3-5-19(17)32(12-21(26)27)20-6-4-15(25)10-18(20)30-22/h3-6,9-10,13,16,21H,7-8,11-12H2,1-2H3,(H,28,33)(H,29,30)/t16-/m0/s1
Molecular weight 479.17 Da
AlogP 0.0
HBond acceptors 6
HBond donors 2
Atoms 58

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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

Expert Reviews

by SERP
(on 18 Mar 2017 )
Cellular Use Rating
In Model Organisms
NVS-PAK1-1 is a potent PAK1 inhibitor with exclusive selectivity for this kinase. Structural studies revealed an allosteric binding mode. This inhibitor is highly potent in cellular assays but showed...
by SERP
(on 18 Mar 2017 )
Cellular Use Rating
In Model Organisms
NVS-PAK1-1 is a potent, allosteric PAK1 inhibitor. It is about 60-fold selective over PAK2. It is highly selective over other kinases in the kinome. It has a submicromolar IC50 in a PAK1 autophosphorylation...
by SERP
(on 19 Mar 2017 )
Cellular Use Rating
In Model Organisms
Rudolph et al., J Med Chem 2016 demonstrate that class I PAK inhibitors from two structurally distinct classes reveal persistent cardiovascular toxicity and correlate minimum toxic concentrations with...

Portal Comments

...

(last updated: 7 Nov 2023)

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