Identification
NameVX-702
Accession NumberDB05470
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External IDs Not Available
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII527E7SK68P
CAS numberNot Available
WeightAverage: 404.325
Monoisotopic: 404.089638294
Chemical FormulaC19H12F4N4O2
InChI KeyFYSRKRZDBHOFAY-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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Mitogen-activated protein kinase 14ProteinunknownNot AvailableHumanQ16539 details
Tumor necrosis factorProteinunknownNot AvailableHumanP01375 details
Interleukin-1 betaProteinunknownNot AvailableHumanP01584 details
Interleukin-6ProteinunknownNot AvailableHumanP05231 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

good tolerability with three months of treatment,

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentRheumatoid Arthritis2
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPhenylpyridines
Direct ParentPhenylpyridines
Alternative ParentsN-phenylureas / Nicotinamides / Fluorobenzenes / Imidolactams / Aryl fluorides / Heteroaromatic compounds / Ureas / Primary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds
Substituents2-phenylpyridine / N-phenylurea / Nicotinamide / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / Fluorobenzene / Halobenzene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot 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 cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad r...
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 action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
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, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.
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 Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as ...
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 June 14, 2017 10:31