elacridar   Click here for help

GtoPdb Ligand ID: 13578

Synonyms: GF-120918 | GF120918 | GG918 [7] | GW-120918 | GW120918
PDB Ligand
Compound class: Synthetic organic
Comment: Elacridar (GF120918) is a dual inhibitor of P-glycoprotein (ABCB1; MDR protein 1) and breast cancer resistance protein (BCRP; ABCG2) [4] [2-3]. These proteins are efflux transporters that are associated with resistance to chemotherapeutic drugs in tumours. Elacridar is a third-generation allosteric (non-competitive) ABCB1 inhibitor.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

elacridar is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 89.13
Molecular weight 563.64
XLogP 2.44
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COC1=C2C(=CC=C1)C(=O)C3=CC=CC(=C3N2)C(=O)NC4=CC=C(C=C4)CCN5CCC6=C(C=C(C(=C6)OC)OC)C5
Isomeric SMILES COC1=CC=CC2=C1NC3=C(C2=O)C=CC=C3C(=O)NC4=CC=C(C=C4)CCN5CCC6=CC(=C(C=C6C5)OC)OC
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)
InChI Key OSFCMRGOZNQUSW-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Horie K, Tang F, Borchardt RT. (2003)
Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter.
Pharm Res, 20 (2): 161-8. [PMID:12636153]
2. Hyafil F, Vergely C, Du Vignaud P, Grand-Perret T. (1993)
In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative.
Cancer Res, 53 (19): 4595-602. [PMID:8402633]
3. Kruijtzer CM, Beijnen JH, Rosing H, ten Bokkel Huinink WW, Schot M, Jewell RC, Paul EM, Schellens JH. (2002)
Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918.
J Clin Oncol, 20 (13): 2943-50. [PMID:12089223]
4. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH. (2001)
Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.
Clin Cancer Res, 7 (4): 935-41. [PMID:11309344]
5. Ochoa-Puentes C, Bauer S, Kühnle M, Bernhardt G, Buschauer A, König B. (2013)
Benzanilide-Biphenyl Replacement: A Bioisosteric Approach to Quinoline Carboxamide-Type ABCG2 Modulators.
ACS Med Chem Lett, 4 (4): 393-6. [PMID:24900683]
6. Puentes CO, Höcherl P, Kühnle M, Bauer S, Bürger K, Bernhardt G, Buschauer A, König B. (2011)
Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2).
Bioorg Med Chem Lett, 21 (12): 3654-7. [PMID:21570282]
7. Witherspoon SM, Emerson DL, Kerr BM, Lloyd TL, Dalton WS, Wissel PS. (1996)
Flow cytometric assay of modulation of P-glycoprotein function in whole blood by the multidrug resistance inhibitor GG918.
Clin Cancer Res, 2 (1): 7-12. [PMID:9816083]