Explore a selection of our essential drug information below, or:
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
Structure for Elacridar (DB04881)
- 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.
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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.
Target Actions Organism AATP-dependent translocase ABCB1 inhibitorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Elacridar. Afatinib The serum concentration of Afatinib can be increased when it is combined with Elacridar. Allopurinol Elacridar may decrease the excretion rate of Allopurinol which could result in a higher serum level. Alpelisib The serum concentration of Alpelisib can be increased when it is combined with Elacridar. Ambrisentan The serum concentration of Ambrisentan can be increased when it is combined with Elacridar. - Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Elacridar hydrochloride NX2BHH1A5B 143851-98-3 IQOJZZHRYSSFJM-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
- 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]
- 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]
- External Links
- KEGG Drug
- D03968
- PubChem Compound
- 119373
- PubChem Substance
- 175426884
- ChemSpider
- 106620
- BindingDB
- 50206310
- ChEMBL
- CHEMBL396298
- ZINC
- ZINC000003915436
- PDBe Ligand
- R0Z
- PDB Entries
- 7a6c / 8y6h / 8y6i
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Leukemias / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.00281 mg/mL ALOGPS logP 5.46 ALOGPS logP 6.81 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 13.88 Chemaxon pKa (Strongest Basic) 8.36 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 89.13 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 165.2 m3·mol-1 Chemaxon Polarizability 63.43 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8334 Blood Brain Barrier + 0.6042 Caco-2 permeable - 0.5842 P-glycoprotein substrate Substrate 0.743 P-glycoprotein inhibitor I Inhibitor 0.9227 P-glycoprotein inhibitor II Inhibitor 0.982 Renal organic cation transporter Non-inhibitor 0.7088 CYP450 2C9 substrate Non-substrate 0.7961 CYP450 2D6 substrate Non-substrate 0.7668 CYP450 3A4 substrate Substrate 0.7789 CYP450 1A2 substrate Non-inhibitor 0.8964 CYP450 2C9 inhibitor Non-inhibitor 0.6245 CYP450 2D6 inhibitor Non-inhibitor 0.9594 CYP450 2C19 inhibitor Non-inhibitor 0.872 CYP450 3A4 inhibitor Inhibitor 0.6329 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7027 Ames test Non AMES toxic 0.649 Carcinogenicity Non-carcinogens 0.9279 Biodegradation Not ready biodegradable 0.9946 Rat acute toxicity 2.3993 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8558 hERG inhibition (predictor II) Inhibitor 0.9543
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 246.5571926 predictedDarkChem Lite v0.1.0 [M-H]- 225.14215 predictedDeepCCS 1.0 (2019) [M+H]+ 246.9512926 predictedDarkChem Lite v0.1.0 [M+H]+ 227.5377 predictedDeepCCS 1.0 (2019) [M+Na]+ 246.1298926 predictedDarkChem Lite v0.1.0 [M+Na]+ 233.45024 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Drug created at October 20, 2007 20:07 / Updated at October 09, 2024 11:44