Tarenflurbil

Identification

Name
Tarenflurbil
Accession Number
DB05289  (DB12936)
Type
Small Molecule
Groups
Investigational
Description

Tarenflurbil is an investigational drug that was studied in patients with mild Alzheimer's disease. It is a selective amyloid lowering agent (SALA) that reduces levels of the toxic peptide amyloid beta 42 (Aβ42) in cultured human cells and in animal models. Aβ42 is the primary initiator of neurotoxicity and amyloid plaque development in the brains of Alzheimer's disease patients. In June 2008 development of the drug for Alzheimer's disease was discontinued. Tarenflurbil has also been used in trials studying the treatment of Prostate Cancer.

Structure
Thumb
Synonyms
  • (−)-(2R)-2-(2-fluorobiphenyl-4-yl)propanoic acid
  • (2R)-2-(2-fluorobiphenyl-4-yl)propanoic acid
  • (R)-2-fluoro-α-methyl(1,1'-biphenyl)-4-acetic acid
  • (R)-flurbiprofen
External IDs
E-7869 / MPC-7869
International/Other Brands
Flurizan
Categories
UNII
501W00OOWA
CAS number
51543-40-9
Weight
Average: 244.2609
Monoisotopic: 244.089957865
Chemical Formula
C15H13FO2
InChI Key
SYTBZMRGLBWNTM-SNVBAGLBSA-N
InChI
InChI=1S/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)/t10-/m1/s1
IUPAC Name
(2R)-2-(3-fluoro-4-phenylphenyl)propanoic acid
SMILES
C[C@@H](C(O)=O)C1=CC(F)=C(C=C1)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in alzheimer's disease and prostate cancer.

Pharmacodynamics
Not Available
Mechanism of action

MPC-7869 is not an inhibitor of cyclooxygenase enzymes (COX-1 and COX-2). The compound modulates the signal transduction and transcription activation pathways associated with nuclear factor kappaB (NFkappaB), a principle transcription factor in the expression of many molecules involved in cell growth, cell death and inflammation. In addition, MPC-7869 has recently been shown to modulate gamma-secretase and selectively lower levels of Abeta42 peptide in vitro and in vivo, and to reduce amyloid pathology in the brain. MPC-7869 has an excellent safety profile and is very potent in animal models of cancer and Alzheimer's disease. In transgenic mouse studies, MPC-7869 reduced brain amyloid levels and prevented memory loss.

TargetActionsOrganism
UNF-kappa-B essential modulatorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
92337
PubChem Substance
175426967
ChemSpider
83361
BindingDB
50172473
ChEBI
38666
ChEMBL
CHEMBL190083
HET
FLR
Wikipedia
Tarenflurbil
PDB Entries
3r94 / 3rr3

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2Unknown StatusTreatmentProstate Cancer1
3CompletedTreatmentAlzheimer's Disease (AD) / Dementias1
3TerminatedTreatmentAlzheimer's Disease (AD)1
3TerminatedTreatmentAlzheimer's Disease (AD) / Dementias1

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 Solubility0.0249 mg/mLALOGPS
logP3.57ALOGPS
logP3.94ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.42ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity67.29 m3·mol-1ChemAxon
Polarizability25.31 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9824
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.76
P-glycoprotein inhibitor INon-inhibitor0.9061
P-glycoprotein inhibitor IINon-inhibitor0.9739
Renal organic cation transporterNon-inhibitor0.912
CYP450 2C9 substrateNon-substrate0.7247
CYP450 2D6 substrateNon-substrate0.9249
CYP450 3A4 substrateNon-substrate0.7205
CYP450 1A2 substrateInhibitor0.8663
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9546
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9674
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8752
Ames testNon AMES toxic0.9659
CarcinogenicityNon-carcinogens0.5554
BiodegradationNot ready biodegradable0.9861
Rat acute toxicity3.1121 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9849
hERG inhibition (predictor II)Non-inhibitor0.9116
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-002b-1910000000-0371815b89a4378bec81

Taxonomy

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
Phenylpropanoic acids / Monocyclic monoterpenoids / Aromatic monoterpenoids / Fluorobenzenes / Aryl fluorides / Monocarboxylic acids and derivatives / Carboxylic acids / Organofluorides / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Biphenyl / 2-phenylpropanoic-acid / P-cymene / Aromatic monoterpenoid / Monocyclic monoterpenoid / Monoterpenoid / Fluorobenzene / Halobenzene / Aryl halide / Aryl fluoride
show 11 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
flurbiprofen (CHEBI:38666)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the i...
Gene Name
IKBKG
Uniprot ID
Q9Y6K9
Uniprot Name
NF-kappa-B essential modulator
Molecular Weight
48197.35 Da

Drug created on November 18, 2007 11:23 / Updated on November 02, 2018 06:09