ELACRIDAR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H33N3O5
Molecular Weight	563.6429
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC)C=C2CN(CCC3=CC=C(NC(=O)C4=C5NC6=C(OC)C=CC=C6C(=O)C5=CC=C4)C=C3)CCC2=C1

InChI

InChIKey=OSFCMRGOZNQUSW-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C34H33N3O5
Molecular Weight	563.6429
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800002537
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB04881

Elacridar is an oral bioenhancer that targets multiple drug resistance in tumors. Elacridar is a strong and relatively specific inhibitor of P-gp and BCRP, two main efflux transporters. Development of elacridar is assumed to have been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
P-glycoprotein 1 54 Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8402633	Inhibitor 8297		70.0 nM [IC50]
ATP-binding cassette sub-family G member 2 16 Target ID: CHEMBL5393 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15930306	Inhibitor 8297		0.31 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800002537 https://www.ncbi.nlm.nih.gov/pubmed/17545533 https://www.ncbi.nlm.nih.gov/pubmed/15565444	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
185 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545533	1000 mg 1 times / week multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	ELACRIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
2629 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545533	1000 mg 1 times / week multiple, oral dose: 1000 mg route of administration: Oral experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	ELACRIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
1000 mg 1 times / week multiple, oral Highest studied dose Dose: 1000 mg, 1 times / week Route: oral Route: multiple Dose: 1000 mg, 1 times / week Co-administed with:: topotecan(1000 mg of elacridar on days 1 and 8 1 h before or simultaneously with 2.0 mg oral topotecan) Sources: https://pubmed.ncbi.nlm.nih.gov/17545533 Page: p.3279	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FED Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/17545533 Page: p.3279	Sources: https://pubmed.ncbi.nlm.nih.gov/17545533 Page: p.3279

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116194	https://www.001chemical.com/chem/search?q=DY116194
1PlusChem LLC	1P001IXZ	https://www.1pchem.com/search?query=1P001IXZ
1PlusChem LLC	1P00AP6W	https://www.1pchem.com/search?query=1P00AP6W
A2B Chem	AE98408	http://a2bchem.com/prod/AE98408
AChemBlock	10315	http://www.achemblock.com/catalogsearch/result/?q=10315
AChemBlock	Q65677	http://www.achemblock.com/catalogsearch/result/?q=Q65677
AK Scientific	7066AA	https://aksci.com/item_detail.php?cat=7066AA
AK Scientific	X2085	https://aksci.com/item_detail.php?cat=X2085
Ambeed	A351095	http://www.ambeed.com/search/Search.html?keyword=A351095
Angene	AGN-PC-0PUNBF	http://www.angenechemical.com/productshow/AGN-PC-0PUNBF.html
ApexBio Technology	A3384	https://www.apexbt.com/catalogsearch/result/?q=A3384
Apollo Scientific	BIE3025	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIE3025&product_group=%25&search_fieldname=header_search
AstaTech	41230	http://astatechinc.com/CPSResult.php?CRNO=41230
Axon MedChem	1896	https://www.axonmedchem.com/product/1896
BOC Sciences	143664-11-3	http://www.bocsci.com/description.asp?cas=143664-11-3
BOC Sciences	143851-98-3	http://www.bocsci.com/description.asp?cas=143851-98-3
Cayman Chemical	18128	http://www.caymanchem.com/app/template/Product.vm/catalog/18128
Chem Scene	CS-1113	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1113
ChemShuttle	110858	https://www.chemshuttle.com/catalogsearch/result/?q=110858
Combi-Blocks	QI-6128	http://www.combi-blocks.com/cgi-bin/find.cgi?QI-6128
Combi-Blocks	QK-4482	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-4482
Excenen	EX-A2228	http://www.excenen.com/searchresultlist.php?id=EX-A2228
KeyOrganics	AS-18773	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-18773
Lab Seeker	SC-83931	http://www.labseeker.com/search.php?keywords=SC-83931&category=0
LabSeeker	SC-83931	http://www.labseeker.com/search.php?keywords=SC-83931&category=0
Matrix Scientific	96115	http://www.matrixscientific.com/096115.html
Matrix Scientific	132494	http://www.matrixscientific.com/132494.html
MedChem Express	HY-50879	https://www.medchemexpress.com/search.html?q=HY-50879&ft=&fa=&fp=
MedChem Express	HY-50880	https://www.medchemexpress.com/search.html?q=HY-50880&ft=&fa=&fp=
MolPort	MolPort-005-943-147	https://www.molport.com/shop/molecule-link/MolPort-005-943-147
MolPort	MolPort-023-332-877	https://www.molport.com/shop/molecule-link/MolPort-023-332-877
MolPort	MolPort-047-116-778	https://www.molport.com/shop/molecule-link/MolPort-047-116-778
Molcore	MC116194	http://www.molcore.com/CatMC116194.html
Molnova	M11856	https://www.molnova.com/en/serch-list.html?keywords=M11856
Molnova	M11860	https://www.molnova.com/en/serch-list.html?keywords=M11860
MuseChem	I006454	https://www.musechem.com/product/I006454.html
MuseChem	R008860	https://www.musechem.com/product/R008860.html
Ryan Scientific	Tyrosol	https://ryansci.com/products?q=Tyrosol&list_q=&search_type=exact
Selleck Chemicals	S7772	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7772
ShangHai Biochempartner	BCP000627	http://www.biochempartner.com/search_BCP000627
ShangHai Biochempartner	BCP05709	http://www.biochempartner.com/search_BCP05709
ShangHai Biochempartner	BCP14056	http://www.biochempartner.com/search_BCP14056
Tocris	4646	https://www.tocris.com/search.php?Type=QuickSearch&Value=4646
Toronto Research Chemicals	E489000	https://www.trc-canada.com/product-detail/?CatNum=E489000
W&J PharmaChem	50C813417	http://wjpharmachem.com/new/searcht.php?keyword=50C813417
eMolecules	104664531	https://orderbb.emolecules.com/search/#?query=104664531
eMolecules	10475114	https://orderbb.emolecules.com/search/#?query=10475114
eMolecules	43366954	https://orderbb.emolecules.com/search/#?query=43366954
eNovation Chemicals	D501763	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501763&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3715841817	https://mcule.com/MCULE-3715841817/
mcule	MCULE-6352522634	https://mcule.com/MCULE-6352522634/

PubMed

Title	Date	PubMed
Differentiation of gut and hepatic first pass metabolism and secretion of saquinavir in ported rabbits.	2004 Jul	15004217
Multiple mechanisms are involved in the biliary excretion of acetaminophen sulfate in the rat: role of Mrp2 and Bcrp1.	2005 Aug	15860656
Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2.	2005 Jun 1	15930306
Comparison of drug efflux transport kinetics in various blood-brain barrier models.	2006 Jun	16554372
Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine.	2007 Jul	17437964
P-glycoprotein-mediated active efflux of the anti-HIV1 nucleoside abacavir limits cellular accumulation and brain distribution.	2007 Nov	17709369
Mechanisms underlying saturable intestinal absorption of metformin.	2008 Aug	18458049
Investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) on pharmacokinetics and central nervous system penetration of abacavir and zidovudine in the mouse.	2008 Aug	18443033
N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) as a chemical ATP-binding cassette transporter family G member 2 (Abcg2) knockout model to study nitrofurantoin transfer into milk.	2008 Dec	18799806
P-glycoprotein restricts the penetration of oseltamivir across the blood-brain barrier.	2008 Feb	18039806
Kinetic identification of membrane transporters that assist P-glycoprotein-mediated transport of digoxin and loperamide through a confluent monolayer of MDCKII-hMDR1 cells.	2008 Feb	17967933
Multidrug resistance-associated protein 2 is primarily responsible for the biliary excretion of fexofenadine in mice.	2008 Jan	17913796
Small P-gp modulating molecules: SAR studies on tetrahydroisoquinoline derivatives.	2008 Jan 1	17936633
Role of P-glycoprotein and the intestine in the excretion of DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide] in rodents.	2008 Jun	18347085
Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice.	2008 May	17932689
Apparent differences in mechanisms of harmol sulfate biliary excretion in mice and rats.	2008 Nov	18719241
Development and characterisation of a new model of rat trophoblasts.	2009 Feb	19013229
Cross-functioning between the extraneuronal monoamine transporter and multidrug resistance protein 1 in the uptake of adrenaline and export of 5-(glutathion-S-yl)adrenaline in rat cardiomyocytes.	2009 Jan	19053318
Substrate-dependent breast cancer resistance protein (Bcrp1/Abcg2)-mediated interactions: consideration of multiple binding sites in in vitro assay design.	2009 Mar	19056916
Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux.	2012 May 1	22464980

Patents

Sample Use Guides

In Vivo Use Guide

The starting daily dose of GF120918 was 50 mg and was to be increased in subsequent cohorts until a steady state plasma level of 100 ng/ml was reached.

Route of Administration: Oral

In Vitro Use Guide

In Caki-1 and ACHN cells, elacridar ( 2.5 μM) significantly inhibits the cell growth. The P-glycoprotein expression is found to be inhibited by 5 uM elacridar in all cell lines (786-O, ACHN, and Caki-1).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:39:11 GMT 2023` Edited by `admin` on `Fri Dec 15 15:39:11 GMT 2023`
Record UNII	N488540F94
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ELACRIDAR

Official Name

English

elacridar [INN]

Common Name

English

4-ACRIDINECARBOXAMIDE, N-(4-(2-(3,4-DIHYDRO-6,7-DIMETHOXY-2(1H)-ISOQUINOLINYL)ETHYL)PHENYL)-9,10-DIHYDRO-5-METHOXY-9-OXO-

Systematic Name

English

Elacridar [WHO-DD]

Common Name

English

LY-335979

Code

English

4'-(2-(3,4-DIHYDRO-6,7-DIMETHOXY-2(1H)-ISOQUINOLYL)ETHYL)-5-METHOXY-9-OXO-4-ACRIDANCARBOXANILIDE

Systematic Name

English

LY335979

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1744