NAV

VX-702

Identification

Generic Name
VX-702
DrugBank Accession Number
DB05470
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 404.325
Monoisotopic: 404.089638294
Chemical Formula
C19H12F4N4O2
Synonyms
Not Available
External IDs
  • VX 702
  • VX-702
  • VX702
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Pharmacology

Indication

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

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Contraindications & Blackbox Warnings
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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 AvailableHumans
UTumor necrosis factorNot AvailableHumans
UInterleukin-1 betaNot AvailableHumans
UInterleukin-6Not AvailableHumans
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

Adverse Effects
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Toxicity

good tolerability with three months of treatment,

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxamide group / Carboxylic acid derivative
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
527E7SK68P
CAS number
745833-23-2
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

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
PubChem Compound
10341154
PubChem Substance
347827732
ChemSpider
8516613
BindingDB
50314071
ChEBI
94489
ChEMBL
CHEMBL1090090
ZINC
ZINC000036377992

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
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)0.042Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area102.31 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity95.36 m3·mol-1Chemaxon
Polarizability34.86 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-MSsplash10-03di-1219000000-c2a6f41b5934c12145a4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01p2-0009000000-723c8c52780d1fabe51a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-0009000000-51b391f208a73c3502e5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000j-0009100000-a8912b26532de1a4f916
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-0009000000-a9db6a128c177c2ac33c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0007-0009000000-4a66ec643ef426f98976
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-9138000000-aa0249890024e70249e0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-184.8035
predicted
DeepCCS 1.0 (2019)
[M+H]+187.1615
predicted
DeepCCS 1.0 (2019)
[M+Na]+193.55109
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Mitogen-activated protein kinase 14
Kind
Protein
Organism
Humans
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
Details2. Tumor necrosis factor
Kind
Protein
Organism
Humans
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
Details3. Interleukin-1 beta
Kind
Protein
Organism
Humans
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
Details4. Interleukin-6
Kind
Protein
Organism
Humans
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 at November 18, 2007 18:25 / Updated at June 12, 2020 16:52