This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification
NameDilmapimod
Accession NumberDB12140  (DB05250)
TypeSmall Molecule
GroupsInvestigational
Description

Dilmapimod has been used in trials studying the treatment and diagnostic of Nerve Trauma, Inflammation, Pain, Neuropathic, Arthritis, Rheumatoid, and Coronary Heart Disease, among others. Dilmapimod (SB-681323) is a p38 MAP-kinase inhibitor that has potential uses in inflammatory conditions such as RA (Rheumatoid Arthritis). Previous p38 MAP-kinase inhibitors have been hindered in development by liver toxicity. Methotrexate (common treatment for RA patients) also has potential liver toxicity.}

Structure
Thumb
SynonymsNot Available
External IDs SB-681323 / SB681323
Product Ingredients
IngredientUNIICASInChI KeyDetails
Dilmapimod tosylate7R1193W65J 937169-00-1ONQKJJNSLLVYHF-UHFFFAOYSA-NDetails
ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
CategoriesNot Available
UNIIQ3238VQW0N
CAS number444606-18-2
WeightAverage: 456.425
Monoisotopic: 456.140924977
Chemical FormulaC23H19F3N4O3
InChI KeyORVNHOYNEHYKJG-UHFFFAOYSA-N
InChI
InChI=1S/C23H19F3N4O3/c1-12-9-13(24)5-6-15(12)20-16-7-8-19(33)30(21-17(25)3-2-4-18(21)26)22(16)29-23(28-20)27-14(10-31)11-32/h2-9,14,31-32H,10-11H2,1H3,(H,27,28,29)
IUPAC Name
8-(2,6-difluorophenyl)-2-[(1,3-dihydroxypropan-2-yl)amino]-4-(4-fluoro-2-methylphenyl)-7H,8H-pyrido[2,3-d]pyrimidin-7-one
SMILES
CC1=CC(F)=CC=C1C1=C2C=CC(=O)N(C2=NC(NC(CO)CO)=N1)C1=C(F)C=CC=C1F
Pharmacology
Indication

Dilmapimod has been used in trials studying the treatment and diagnostic of Nerve Trauma, Inflammation, Pain, Neuropathic, Arthritis, Rheumatoid, and Coronary Heart Disease, among others.

Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action

Dilmapimod reduces the levels of proinflammatory cytokines and chemokines and reduce cellular infiltration to sites of inflammation, thereby reducing local damage. In diseases such as RA and IBD, TNFα blockade through either anti-TNFα antibodies or use of soluble TNFα receptors. Inhibition of p38α offers significant inhibition of TNFα, and cytokines such as IL-1β and IL-6, which offer additional therapeutic efficacy.

TargetKindPharmacological actionActionsOrganismUniProt ID
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
ToxicityNot Available
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. Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P, Naumann M: Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J. 2004 Oct;18(13):1550-2. Epub 2004 Aug 2. [PubMed:15289440 ]
  2. Schindler JF, Monahan JB, Smith WG: p38 pathway kinases as anti-inflammatory drug targets. J Dent Res. 2007 Sep;86(9):800-11. [PubMed:17720847 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticInflammatory Reaction / Rheumatoid Arthritis1
1CompletedTreatmentPulmonary Disease, Chronic Obstructive1
1CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Disease, Chronic Obstructive1
2CompletedTreatmentCoronary Heart Disease (CHD)1
2CompletedTreatmentLung Injury, Acute1
2CompletedTreatmentNerve Trauma / Pain, Neuropathic1
2CompletedTreatmentRheumatoid Arthritis2
Properties
StateNot Available
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0118 mg/mLALOGPS
logP3.03ALOGPS
logP3.6ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)13.38ChemAxon
pKa (Strongest Basic)1.74ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area98.58 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity118 m3·mol-1ChemAxon
Polarizability43.31 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative ParentsPyrido[2,3-d]pyrimidines / Toluenes / Pyridinones / Fluorobenzenes / Aminopyrimidines and derivatives / Aryl fluorides / Heteroaromatic compounds / Lactams / Azacyclic compounds / Primary alcohols
Substituents4-phenylpyrimidine / Pyridopyrimidine / Pyrido[2,3-d]pyrimidine / Aminopyrimidine / Fluorobenzene / Halobenzene / Pyridinone / Toluene / Aryl fluoride / Pyridine
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

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 October 20, 2016 15:26 / Updated on June 11, 2017 21:31