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VX-745 | VX-745 : ATP competitive inhibitor of MAPK14
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

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Targets Biochemical/Biophysical Potency Cellular Potency
MAPK14
  • KD:2.8 nM
  • IC50:45 nM
  • IC50:51 nM
ATP competitive
50-100 nM

Selectivity

In Vitro Selectivity Assessment

Potency: KD - MAPK11 74 nM

Potency Assay Off-Target:
VX-745 was 20-fold selective for MAPK14 (p38alpha) > MAPK11 (p38beta) in IC50 assays. VX-745 was te ...

Potency
Cellular
In Vitro

MAPK14

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/ml2001455

In Vivo Validations

Rat
Dose: 4.8 mg/mL
Route of delivery: Intravenous
Plasma half life: 1.9 h
Systemic clearance: 63 mL/min/kg
Area Under the Curve:: 1.26 μg·h/mL
Volume of Distribution at Steady-State: 3.9 L/Kg

DOI Reference: 10.1021/ml2001455

Dose: 43 mg/Kg
Route of delivery: Oral
Plasma half life: 4.5 h
Cmax: 0.89 μg/mL
Area Under the Curve:: 6.3 μg·h/mL
Bioavailability: 56%

DOI Reference: 10.1021/ml2001455

Mouse
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 2.6 h
Systemic clearance: 21 mL/min/kg
Area Under the Curve:: 1.54 μg·h/mL
Volume of Distribution at Steady-State: 2.2 L/Kg

DOI Reference: 10.1021/ml2001455

Dose: 40 mg/mL
Route of delivery: Oral
Plasma half life: 4.5 h
Cmax: 7.85 μg/mL
Area Under the Curve:: 26.96 μg·h/mL
Bioavailability: 87%

DOI Reference: 10.1021/ml2001455

Dog
Dose: 13.8 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.5 h
Systemic clearance: 39 mL/min/kg
Area Under the Curve:: 6.12 μg·h/mL
Volume of Distribution at Steady-State: 2.3 L/Kg

DOI Reference: 10.1021/ml2001455

Dose: 33 mg/Kg
Route of delivery: Oral
Plasma half life: 4.5 h
Cmax: 1.37 μg/mL
Area Under the Curve:: 4.34 μg·h/mL
Bioavailability: 69%

DOI Reference: 10.1021/ml2001455

Orthogonal Probes def

FS-694
SR-318
Skepinone-L

Chemical Information

Molecular Formula C19H9Cl2F2N3OS
SMILEs O=c1ncn2nc(Sc3ccc(F)cc3F)ccc2c1-c1c(Cl)cccc1Cl
InChI InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H
Molecular weight 434.98 Da
AlogP 5.492700000000003
HBond acceptors 4
HBond donors --
Atoms 37

Vendors

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Expert Reviews

by SERP
(on 23 Jun 2016)
Cellular Use Rating
In Model Organisms
This is a selective probe with some off-target activity against p38β; it is able to cross the blood-brain barrier.
by SERP
(on 1 Jul 2016)
Cellular Use Rating
In Model Organisms
This probe has a pretty good selectivity towards p38alpha with effects on peripheral blood mononuclear cells (PBMCs) and on a rheumatoid arthritis mouse model.
by SERP
(on 3 Jul 2017)
Cellular Use Rating
In Model Organisms
Effective inhibition of p38α should be achievable at concentrations between 50-100 nM. The reported Ki for p38β is 220 nM as determined in α spectrophotometric coupled-enzyme assay using recombinant...
This compound is a fairly selective p38 MAPKα inhibitor with a 20-fold window to p38 MAPKβ based on assessement in an activity assay. It is also useful as an in vivo probe.
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