Identification

Generic Name
Rilapladib
DrugBank Accession Number
DB05119
Background

Rilapladib is the third genomics-derived small molecule drug arising from the Human Genome Sciences-GlaxoSmithKline collaboration to enter clinical development. It is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzyme associated with the formation of atherosclerotic plaques.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 735.81
Monoisotopic: 735.255404085
Chemical Formula
C40H38F5N3O3S
Synonyms
  • Rilapladib
External IDs
  • GSK 659032
  • SB 659032
  • SB-659032

Pharmacology

Indication

Investigated for use/treatment in atherosclerosis and cardiovascular disorders.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Rilapladib is a Lp-PLA2 inhibitor. Lp-PLA2 has been found to be enriched in the highly atherogenic lipoprotein subfraction of small dense LDL, which is susceptible to oxidative modification. Moreover, enzyme levels are increased in patients with hyperlipidaemia, stroke, Type 1 and Type 2 diabetes mellitus, as well as in post-menopausal women. As such, plasma Lp-PLA2 levels tend to be elevated in those individuals who are considered to be at risk of developing accelerated atherosclerosis and clinical cardiovascular events. Thus, inhibition of the Lp-PLA2 enzyme would be expected to stop the build up of this fatty streak (by inhibition of the formation of lysophosphatidylcholine), and so be useful in the treatment of atherosclerosis.

TargetActionsOrganism
UPlatelet-activating factor acetylhydrolaseNot 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

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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 biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Hydroquinolones / Trifluoromethylbenzenes / Hydroquinolines / Alkylarylthioethers / Fluorobenzenes / Vinylogous thioesters / Pyridines and derivatives / Piperidines / Aryl fluorides / Vinylogous amides
show 12 more
Substituents
Alkyl fluoride / Alkyl halide / Alkylarylthioether / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Aryl thioether / Azacycle
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
O14CWE893Z
CAS number
412950-08-4
InChI Key
NNBGCSGCRSCFEA-UHFFFAOYSA-N
InChI
InChI=1S/C40H38F5N3O3S/c1-51-22-21-46-19-17-32(18-20-46)47(24-27-9-11-28(12-10-27)29-13-15-31(16-14-29)40(43,44)45)37(50)25-48-35-8-3-2-6-33(35)36(49)23-38(48)52-26-30-5-4-7-34(41)39(30)42/h2-16,23,32H,17-22,24-26H2,1H3
IUPAC Name
2-(2-{[(2,3-difluorophenyl)methyl]sulfanyl}-4-oxo-1,4-dihydroquinolin-1-yl)-N-[1-(2-methoxyethyl)piperidin-4-yl]-N-{[4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]methyl}acetamide
SMILES
COCCN1CCC(CC1)N(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C(SCC2=C(F)C(F)=CC=C2)=CC(=O)C2=C1C=CC=C2

References

General References
Not Available
PubChem Compound
9918381
PubChem Substance
347827712
ChemSpider
8094027
BindingDB
50205805
ChEMBL
CHEMBL2104981
ZINC
ZINC000003973276

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAtherosclerosis1
1CompletedDiagnosticAtherosclerosis / Healthy Subjects (HS)1
1CompletedTreatmentAtherosclerosis2
1WithdrawnTreatmentAlzheimer's Disease (AD)1

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 Solubility0.000509 mg/mLALOGPS
logP6.34ALOGPS
logP8.08ChemAxon
logS-6.2ALOGPS
pKa (Strongest Acidic)13.77ChemAxon
pKa (Strongest Basic)8.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area53.09 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity206.32 m3·mol-1ChemAxon
Polarizability72.71 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Phospholipid binding
Specific Function
Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the...
Gene Name
PLA2G7
Uniprot ID
Q13093
Uniprot Name
Platelet-activating factor acetylhydrolase
Molecular Weight
50076.99 Da

Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51