Identification

Generic Name
Elacridar
DrugBank Accession Number
DB04881
Background

Elacridar (GW120918) is an oral bioenhancer that targets multiple drug resistance in tumors. In many cases, the appearance of multidrug resistance in cancer is due to a change in expression of protein inhibitors. As of August 2007 elacridar was not listed on GSK's product pipeline. Development is assumed to have been discontinued.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 563.6429
Monoisotopic: 563.242021181
Chemical Formula
C34H33N3O5
Synonyms
  • Elacridar
External IDs
  • LY-335979
  • LY335979

Pharmacology

Indication

For the treatment of solid tumors.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Elacridar is an oral bioenhancer that targets multiple drug resistance in tumors. In many cases, the appearance of multidrug resistance in cancer is due to a change in expression of protein inhibitors.

Mechanism of action

P-glycoprotein is a well characterized human ABC-transporter of the MDR/TAP subfamily. It is an ATP-dependent efflux pump with broad substrate specificity. It likely evolved as a defence mechanism against harmful substances. Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, therapeutic plasma concentrations are not attained. Elacridar functions by inhibiting P-glycoprotein, resulting in an increased bioavailability of coadminstered drugs.

TargetActionsOrganism
UP-glycoprotein 1Not 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
Adverseeffects
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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.
DrugInteraction
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Elacridar.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Elacridar.
AllopurinolElacridar may decrease the excretion rate of Allopurinol which could result in a higher serum level.
AlpelisibThe serum concentration of Alpelisib can be increased when it is combined with Elacridar.
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Elacridar.
ApixabanElacridar may decrease the excretion rate of Apixaban which could result in a higher serum level.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Elacridar.
AvatrombopagThe serum concentration of Avatrombopag can be increased when it is combined with Elacridar.
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Elacridar.
BaricitinibThe serum concentration of Baricitinib can be increased when it is combined with Elacridar.
Interactions
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Elacridar hydrochlorideNX2BHH1A5B143851-98-3IQOJZZHRYSSFJM-UHFFFAOYSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as acridones. These are acridines containing a ketone group attached to the C9 carbon atom of the acridine moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridones
Alternative Parents
Aromatic anilides / Quinoline carboxamides / Hydroquinolones / Hydroquinolines / Tetrahydroisoquinolines / Phenethylamines / Anisoles / Alkyl aryl ethers / Aralkylamines / Pyridines and derivatives
show 9 more
Substituents
Acridone / Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aralkylamine / Aromatic anilide / Aromatic heteropolycyclic compound / Azacycle / Benzenoid
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
N488540F94
CAS number
143664-11-3
InChI Key
OSFCMRGOZNQUSW-UHFFFAOYSA-N
InChI
InChI=1S/C34H33N3O5/c1-40-28-9-5-7-26-32(28)36-31-25(33(26)38)6-4-8-27(31)34(39)35-24-12-10-21(11-13-24)14-16-37-17-15-22-18-29(41-2)30(42-3)19-23(22)20-37/h4-13,18-19H,14-17,20H2,1-3H3,(H,35,39)(H,36,38)
IUPAC Name
N-{4-[2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]phenyl}-5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxamide
SMILES
COC1=CC=CC2=C1NC1=C(C=CC=C1C(=O)NC1=CC=C(CCN3CCC4=CC(OC)=C(OC)C=C4C3)C=C1)C2=O

References

General References
  1. Hubensack M, Muller C, Hocherl P, Fellner S, Spruss T, Bernhardt G, Buschauer A: Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice. J Cancer Res Clin Oncol. 2008 May;134(5):597-607. Epub 2007 Oct 12. [Article]
  2. Colabufo NA, Berardi F, Cantore M, Perrone MG, Contino M, Inglese C, Niso M, Perrone R, Azzariti A, Simone GM, Porcelli L, Paradiso A: Small P-gp modulating molecules: SAR studies on tetrahydroisoquinoline derivatives. Bioorg Med Chem. 2008 Jan 1;16(1):362-73. Epub 2007 Sep 25. [Article]
KEGG Drug
D03968
PubChem Compound
119373
PubChem Substance
175426884
ChemSpider
106620
BindingDB
50206310
ChEMBL
CHEMBL396298
ZINC
ZINC000003915436
PDBe Ligand
R0Z
PDB Entries
7a6c

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes (MDS)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 Solubility0.00281 mg/mLALOGPS
logP5.46ALOGPS
logP6.81ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)12.06ChemAxon
pKa (Strongest Basic)8.35ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area89.13 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity165.2 m3·mol-1ChemAxon
Polarizability63.43 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8334
Blood Brain Barrier+0.6042
Caco-2 permeable-0.5842
P-glycoprotein substrateSubstrate0.743
P-glycoprotein inhibitor IInhibitor0.9227
P-glycoprotein inhibitor IIInhibitor0.982
Renal organic cation transporterNon-inhibitor0.7088
CYP450 2C9 substrateNon-substrate0.7961
CYP450 2D6 substrateNon-substrate0.7668
CYP450 3A4 substrateSubstrate0.7789
CYP450 1A2 substrateNon-inhibitor0.8964
CYP450 2C9 inhibitorNon-inhibitor0.6245
CYP450 2D6 inhibitorNon-inhibitor0.9594
CYP450 2C19 inhibitorNon-inhibitor0.872
CYP450 3A4 inhibitorInhibitor0.6329
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7027
Ames testNon AMES toxic0.649
CarcinogenicityNon-carcinogens0.9279
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.3993 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8558
hERG inhibition (predictor II)Inhibitor0.9543
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 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

Drugtargets2
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Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Hubensack M, Muller C, Hocherl P, Fellner S, Spruss T, Bernhardt G, Buschauer A: Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice. J Cancer Res Clin Oncol. 2008 May;134(5):597-607. Epub 2007 Oct 12. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created at October 20, 2007 20:07 / Updated at December 04, 2021 10:44