Identification

Name
VX-702
Accession Number
DB05470
Type
Small Molecule
Groups
Investigational
Description

VX-702 is a small molecule investigational oral anti-cytokine therapy for treatment of inflammatory diseases, specifically rheumatoid arthritis (RA). It acts as a p38 MAP kinase inhibitor. In the future, VX-702 may be investigated for combination with methotrexate, a commonly used therapy for RA.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
527E7SK68P
CAS number
Not Available
Weight
Average: 404.325
Monoisotopic: 404.089638294
Chemical Formula
C19H12F4N4O2
InChI Key
FYSRKRZDBHOFAY-UHFFFAOYSA-N
InChI
InChI=1S/C19H12F4N4O2/c20-9-4-5-10(14(23)8-9)16-11(18(24)28)6-7-15(26-16)27(19(25)29)17-12(21)2-1-3-13(17)22/h1-8H,(H2,24,28)(H2,25,29)
IUPAC Name
2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide
SMILES
NC(=O)N(C1=CC=C(C(N)=O)C(=N1)C1=CC=C(F)C=C1F)C1=C(F)C=CC=C1F

Pharmacology

Indication

Investigated for use/treatment in coronary artery disease, inflammatory disorders (unspecified), and rheumatoid arthritis.

Structured Indications
Not Available
Pharmacodynamics

VX-703 is an anti-cytokine therapy in which p38 MAP kinase inhibitor effectively inhibits LPS-stimulated TNF|[alpha]|, IL-6 and IL-1|[beta]| production.

Mechanism of action

This p38 MAP kinase inhibitor effectively inhibits LPS-stimulated TNF|[alpha]|, IL-6 and IL-1|[beta]| production.

TargetActionsOrganism
UMitogen-activated protein kinase 14Not AvailableHuman
UTumor necrosis factorNot AvailableHuman
UInterleukin-1 betaNot AvailableHuman
UInterleukin-6Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

good tolerability with three months of treatment,

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Ding C: Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome. Curr Opin Investig Drugs. 2006 Nov;7(11):1020-5. [PubMed:17117592]
  2. Lee MR, Dominguez C: MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Curr Med Chem. 2005;12(25):2979-94. [PubMed:16378500]
  3. Dominguez C, Powers DA, Tamayo N: p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel. 2005 Jul;8(4):421-30. [PubMed:16022178]
  4. Kuliopulos A, Mohanlal R, Covic L: Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost. 2004 Dec;92(6):1387-93. [PubMed:15583748]
External Links
PubChem Compound
10341154
PubChem Substance
347827732
ChemSpider
8516613
BindingDB
50314071
ChEBI
94489
ChEMBL
CHEMBL1090090

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentRheumatoid Arthritis2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00245 mg/mLALOGPS
logP2.91ALOGPS
logP3.23ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)13.95ChemAxon
pKa (Strongest Basic)-0.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area102.31 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity95.36 m3·mol-1ChemAxon
Polarizability34.71 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Phenylpyridines
Direct Parent
Phenylpyridines
Alternative Parents
N-phenylureas / Nicotinamides / Fluorobenzenes / Imidolactams / Aryl fluorides / Heteroaromatic compounds / Ureas / Primary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds
show 5 more
Substituents
2-phenylpyridine / N-phenylurea / Nicotinamide / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / Fluorobenzene / Halobenzene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da

Drug created on November 18, 2007 11:25 / Updated on December 01, 2017 15:36