ZOSUQUIDAR

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H31F2N3O2
Molecular Weight	527.6042
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@@H](COC1=CC=CC2=C1C=CC=N2)CN3CCN(CC3)[C@@H]4C5=C(C=CC=C5)[C@@H]6[C@H](C7=C4C=CC=C7)C6(F)F

InChI

InChIKey=IHOVFYSQUDPMCN-DBEBIPAYSA-N

InChI=1S/C32H31F2N3O2/c33-32(34)29-22-7-1-3-9-24(22)31(25-10-4-2-8-23(25)30(29)32)37-17-15-36(16-18-37)19-21(38)20-39-28-13-5-12-27-26(28)11-6-14-35-27/h1-14,21,29-31,38H,15-20H2/t21-,29-,30+,31-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C32H31F2N3O2
Molecular Weight	527.6042
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8797588
Curator's Comment: Description was created based on several sources, including

Zosuquidar (LY-335979) is an experimental antineoplastic drug. It is is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. Zosuqidar was initially characterized by Syntex Corporation, which was acquired by Roche in 1990. Roche licensed the drug to Eli Lilly in 1997. It was granted orphan drug status by the FDA in 2006 for AML. Zosuquidar Trihydrochloride had been in phase III clinical trials by Kanisa Pharmaceuticals for the treatment of acute myeloid leukaemia. However, this research has been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
P-glycoprotein 1 54 Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8797588	Inhibitor 8504		60.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute myeloid leukemia 141 Sources: http://adisinsight.springer.com/drugs/800005159 https://clinicaltrials.gov/ct2/show/NCT00046930	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
0.31 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15809877	300 mg/m² 2 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: VINORELBINE	VINORELBINE	ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
427 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15161679	480 mg/m² 1 times / day multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1111 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15809877	300 mg/m² 2 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: VINORELBINE	VINORELBINE	ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
19400 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15161679	480 mg/m² 1 times / day multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15809877	300 mg/m² 2 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: VINORELBINE	VINORELBINE	ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
17 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15161679	480 mg/m² 1 times / day multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		ZOSUQUIDAR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg/m2 2 times / day multiple, oral MTD Dose: 300 mg/m2, 2 times / day Route: oral Route: multiple Dose: 300 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15809877	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/15809877	DLT: febrile neutropeni... Other AEs: Stomatitis, Neutropenia... Dose limiting toxicities: febrile neutropeni (grade 4, 33.3%) Other AEs: Stomatitis (grade 3) Neutropenia (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/15809877

AEs

AE	Significance	Dose	Population
Neutropenia	grade 3	300 mg/m2 2 times / day multiple, oral MTD Dose: 300 mg/m2, 2 times / day Route: oral Route: multiple Dose: 300 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15809877	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/15809877
Stomatitis	grade 3	300 mg/m2 2 times / day multiple, oral MTD Dose: 300 mg/m2, 2 times / day Route: oral Route: multiple Dose: 300 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15809877	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/15809877
febrile neutropeni	grade 4, 33.3% DLT	300 mg/m2 2 times / day multiple, oral MTD Dose: 300 mg/m2, 2 times / day Route: oral Route: multiple Dose: 300 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15809877	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/15809877

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 926 MRP1 116 BCRP 910 CYP1A2 2153 P-gp 1741 MRP2 499	CYP3A 220

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/	likely [Inhibition 50 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22359351/	no
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/	no
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681697	yes [IC50 10.684 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681697	yes [Ki 12.3 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/	yes [Ki 25.3 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10411602/	yes [Ki 3.8 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29440498/ \| https://pubmed.ncbi.nlm.nih.gov/10411602/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 220	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9443851/	likely

PubMed

Title	Date	PubMed
Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999.	2010-11-18	20716770
PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line.	2010-09	20041327
Gateways to clinical trials.	2010-04-13	20383346
Challenges in treating older patients with acute myeloid leukemia.	2010	20628485
A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen.	2009-09	19241078
A phase I trial of continuous infusion of the multidrug resistance inhibitor zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia.	2009-08	19108889
Influence of the dual ABCB1 and ABCG2 inhibitor tariquidar on the disposition of oral imatinib in mice.	2009-07-10	19591692
P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients.	2009-06-23	19549303
Leukemic blast and natural killer cell P-glycoprotein function and inhibition in a clinical trial of zosuquidar infusion in acute myeloid leukemia.	2009-06	18976810
Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors.	2009-04	19139163
Resistance to chemotherapy: new treatments and novel insights into an old problem.	2008-08-05	18665178
Gateways to clinical trials.	2008-04	18597009
Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors.	2008-03-11	18253130
ABC transporters and the accumulation of imatinib and its active metabolite CGP74588 in rat C6 glioma cells.	2008-03	18337118
Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML).	2008-02-13	18271955
Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier.	2007-09	17696988
Inhibition of P-glycoprotein activity at the primate blood-brain barrier increases the distribution of nelfinavir into the brain but not into the cerebrospinal fluid.	2007-09	17591677
Modulation of the brain distribution of imatinib and its metabolites in mice by valspodar, zosuquidar and elacridar.	2007-09	17380257
Pharmacological strategies for overcoming multidrug resistance.	2006-07	16842217
Dependence of nelfinavir brain uptake on dose and tissue concentrations of the selective P-glycoprotein inhibitor zosuquidar in rats.	2006-04	16434546
Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours.	2005-08	15809877
Potential for improvement of docetaxel-based chemotherapy: a pharmacological review.	2005-07-25	16012521
Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar.	2005-07-11	15942626
Modulation of drug resistance transporters as a strategy for treating myelodysplastic syndrome.	2004-12	15494300
Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies.	2004-11-01	15534095
A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxorubicin in patients with advanced malignancy.	2004-05-15	15161679
Bioanalysis of zosuquidar trihydrochloride (LY335979) in small volumes of human and murine plasma by ion-pairing reversed-phase high-performance liquid chromatography.	2003-12-05	14630360
A population pharmacokinetic model for paclitaxel in the presence of a novel P-gp modulator, Zosuquidar Trihydrochloride (LY335979).	2003-07	12848775

Patents

Sample Use Guides

In Vivo Use Guide

Zosuquidar 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3.

Route of Administration: Intravenous

In Vitro Use Guide

Zosuquidar (LY-335979) alone shows the cytotoxicity to drug-sensitive and MDR cell lines with IC50 ranging from 6 uM-16 uM and produces its ability to completely reverse the resistance of the oncolytics (vinblastine, doxorubicin, or etoposide) to the MDR cell lines P388/ADR, MCF7/ADR, 2780AD, or UCLA-P3.003VLB at concentration of 0.1 and 0.5 uM

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:28:04 GMT 2025` Edited by `admin` on `Mon Mar 31 18:28:04 GMT 2025`
Record UNII	AB5K82X98Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZOSUQUIDAR [MI]

Preferred Name

English

ZOSUQUIDAR

Official Name

English

zosuquidar [INN]

Common Name

English

Zosuquidar [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1744