Zosuquidar

MDR modulator CAS# 167354-41-8

Zosuquidar

Catalog No. BCC2074----Order now to get a substantial discount!

Product Name & Size Price Stock
Zosuquidar: 5mg $115 In Stock
Zosuquidar: 10mg Please Inquire In Stock
Zosuquidar: 20mg Please Inquire Please Inquire
Zosuquidar: 50mg Please Inquire Please Inquire
Zosuquidar: 100mg Please Inquire Please Inquire
Zosuquidar: 200mg Please Inquire Please Inquire
Zosuquidar: 500mg Please Inquire Please Inquire
Zosuquidar: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of Zosuquidar

Number of papers citing our products

Chemical structure

Zosuquidar

3D structure

Chemical Properties of Zosuquidar

Cas No. 167354-41-8 SDF Download SDF
PubChem ID 3036703 Appearance Powder
Formula C32H31F2N3O2 M.Wt 527.6
Type of Compound N/A Storage Desiccate at -20°C
Synonyms LY335979
Solubility DMSO : 8.33 mg/mL (15.79 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (insoluble)
Chemical Name (2R)-1-[4-[(2R,4S)-3,3-difluoro-11-tetracyclo[10.4.0.02,4.05,10]hexadeca-1(16),5,7,9,12,14-hexaenyl]piperazin-1-yl]-3-quinolin-5-yloxypropan-2-ol
SMILES C1CN(CCN1CC(COC2=CC=CC3=C2C=CC=N3)O)C4C5=CC=CC=C5C6C(C6(F)F)C7=CC=CC=C47
Standard InChIKey IHOVFYSQUDPMCN-XAKVHENESA-N
Standard InChI 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
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Zosuquidar

DescriptionZosuquidar (LY335979) is a potent negative modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. IC50 value: 60 nM (Ki) Target: P-glycoprotein Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multidrug resistance with Ki of 60 nM. Zosuquidar binds with high affinity to P-glycoprotein and inhibits P-glycoprotein-mediated multidrug resistance (MDR). P-glycoprotein, encoded by the MDR-1 gene, is a member of the ATP-binding cassette superfamily of transmembrane transporters and prevents the intracellular accumulation of many natural product-derived cytotoxic agents. Zosuquidar is a compound of antineoplastic drug candidates currently under development.

References:
[1]. Dantzig AH, et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res. 1996 Sep 15;56(18):4171-9. [2]. Marcelletti JF, Multani PS, Lancet JE et al. Leukemic blast and natural killer cell P-glycoprotein function and inhibition in a clinical trial of zosuquidar infusion in acute myeloid leukemia. Leuk Res. 2009 Jun;33(6):769-74. [3]. Ruff P, Vorobiof DA, Jordaan JP et al. 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. Cancer Chemother Pharmacol. 2009 Sep;64(4):763-8. [4]. Cripe LD, Uno H, Paietta EM et al. 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. Blood. 2010 Nov 18;116(20):4077-85. [5]. Abu Ajaj K, Graeser R, Kratz F. Zosuquidar and an albumin-binding prodrug of zosuquidar reverse multidrug resistance in breast cancer cells of doxorubicin and an albumin-binding prodrug of doxorubicin. Breast Cancer Res Treat. 2012 Jul;134(1):117-29.

Zosuquidar Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Zosuquidar Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Zosuquidar

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.8954 mL 9.4769 mL 18.9538 mL 37.9075 mL 47.3844 mL
5 mM 0.3791 mL 1.8954 mL 3.7908 mL 7.5815 mL 9.4769 mL
10 mM 0.1895 mL 0.9477 mL 1.8954 mL 3.7908 mL 4.7384 mL
50 mM 0.0379 mL 0.1895 mL 0.3791 mL 0.7582 mL 0.9477 mL
100 mM 0.019 mL 0.0948 mL 0.1895 mL 0.3791 mL 0.4738 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Zosuquidar

Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multidrug resistance with Ki of 60 nM. Zosuquidar binds with high affinity to P-glycoprotein and inhibits P-glycoprotein-mediated multidrug resistance (MDR).

Featured Products
New Products
 

References on Zosuquidar

Zosuquidar and an albumin-binding prodrug of zosuquidar reverse multidrug resistance in breast cancer cells of doxorubicin and an albumin-binding prodrug of doxorubicin.[Pubmed:22228402]

Breast Cancer Res Treat. 2012 Jul;134(1):117-29.

The P-glycoprotein (P-gp) is a 170-kDa protein that acts as an energy dependent, transmembrane efflux pump and is encoded by the MDR1 gene. It has been shown to be responsible for multidrug resistance (MDR) in a defined subpopulation of breast cancer patients and thus represents a molecular target for circumventing MDR in this tumor indication. MDR modulators have been developed and demonstrated high selectivity for P-gp with inhibitory activities in the low nanomolar range. Although some objective responses were achieved in clinical trials, combination therapy with these MDR modulators, such as Ca2+ antagonists caused unacceptable toxicity. Targeting P-gp inhibitors to the tumor site is a mean to increase their therapeutic index, and in this context binding of tailor-made prodrugs to circulating albumin is an established technology to reduce the toxicity and enhance the efficacy of anticancer drugs. In this study, we consequently developed an acid-sensitive albumin-binding prodrug of the P-gp inhibitor Zosuquidar (LY335979) in a two-step synthesis using a maleimide hydrazone linker system established in our laboratory that first introduces acetylbenzoic acid at the HO-group of Zosuquidar followed by derivatization with 6-maleimidocaproyl hydrazide to form the acid-sensitive hydrazone bond. The maleimide group enables the prodrug to bind rapidly and selectively to the cysteine-34 position of endogenous albumin after intravenous administration. HPLC analysis demonstrated rapid albumin binding of the Zosuquidar prodrug as well as the quantitative release of the acetylbenzoic ester derivative of Zosuquidar at pH 5.0. Subsequently, its ability to circumvent MDR was tested in two doxorubicin-resistant breast carcinoma cell lines (MCF-7/ADR and MT-3/ADR). The MDR status of these cell lines can be reversed by Zosuquidar which was confirmed in a rhodamine 123 assay using fluorescence microscopy and FACS analysis. Furthermore, Zosuquidar as well its acid-sensitive albumin conjugate re-sensitized cells to doxorubicin as well as to an albumin-binding prodrug of doxorubicin, i.e., the 6-maleimidocaproyl hydrazone derivative of doxorubicin, achieving IC50 values in the same order of magnitude as the parental cell lines. Thus, a novel formulation of Zosuquidar has been developed that could have the potential to improve the toxicity issues and tumor targeting properties of the original compound.

Triggering of Suicidal Erythrocyte Death by Zosuquidar.[Pubmed:26646161]

Cell Physiol Biochem. 2015;37(6):2355-65.

BACKGROUND: The P-glycoprotein inhibitor Zosuquidar (LY335979) is clinically used to augment the effect of cytostatic drugs on suicidal tumor cell death or apoptosis. The present study explored whether the substance is cytotoxic to erythrocytes. Upon injury, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), oxidative stress and activation of several kinases, such as p38 kinase and protein kinase C. METHODS: Phosphatidylserine abundance at the erythrocyte surface was quantified from binding of FITC-labelled annexin-V, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. RESULTS: A 48 h treatment of human erythrocytes with Zosuquidar significantly increased the percentage of annexin-V-binding cells (2 and 4 microg/ml), significantly decreased forward scatter (4 microg/ml), significantly increased [Ca2+]i (4 microg/ml), but did not significantly modify ROS. The up-regulation of annexin-V-binding following Zosuquidar (4 microg/ml) treatment was significantly blunted by removal of extracellular Ca2+, by presence of p38 kinase inhibitor SB203580 (2 microM) and by presence of protein kinase C inhibitor calphostin (100 nM). CONCLUSIONS: Exposure of erythrocytes to Zosuquidar triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect involving Ca2+ entry and requiring activity of SB203580 and calphostin sensitive kinases.

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.[Pubmed:20716770]

Blood. 2010 Nov 18;116(20):4077-85.

Zosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp-mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomized placebo-controlled double-blind trial (Eastern Cooperative Oncology Group 3999). Overall survival was compared between patients receiving conventional-dose cytarabine and daunorubicin and either Zosuquidar (550 mg; 212 patients) or placebo (221 patients). Median and 2-year overall survival values were 7.2 months and 20% on Zosuquidar and 9.4 months and 23% on placebo, respectively (P = .281). Remission rate was 51.9% on Zosuquidar and 48.9% on placebo. All cause mortality to day 42 was not different (Zosuquidar 22.2% vs placebo 16.3%; P = .158). In vitro modulation of P-gp activity by Zosuquidar and expression of P-gp, multidrug resistance-related protein 1, lung resistance protein, and breast cancer resistance protein, were comparable in the 2 arms. Poor-risk cytogenetics were more common in P-gp(+) patients. P-gp expression and cytogenetics were correlated, though independent prognostic factors. We conclude that Zosuquidar did not improve outcome in older acute myeloid leukemia, in part, because of the presence P-gp independent mechanisms of resistance. This trial is registered at www.clinicaltrials.gov as #NCT00046930.

Analysis of the inhibition potential of zosuquidar derivatives on selected bacterial and fungal ABC transporters.[Pubmed:23356389]

Mol Membr Biol. 2013 Mar;30(2):217-27.

The increasing number of multidrug-resistant pathogenic microorganisms is a serious public health issue. Among the multitude of mechanisms that lead to multidrug resistance, the active extrusion of toxic compounds, mediated by MDR efflux pumps, plays an important role. In our study we analyzed the inhibitory capability of 26 synthesized Zosuquidar derivatives on three ABC-type MDR efflux pumps, namely Saccharomyces cerevisiae Pdr5 as well as Lactococcus lactis LmrA and LmrCD. For Pdr5, five compounds could be identified that inhibited rhodamine 6G transport more efficiently than Zosuquidar. One of these is a compound with a new catechol acetal structure that might represent a new lead compound. Furthermore, the determination of IC(50) values for rhodamine 6G transport of Pdr5 with representative compounds reveals values between 0.3 and 0.9 muM. Thus the identified compounds are among the most potent inhibitors known for Pdr5. For the ABC-type efflux pumps LmrA and LmrCD from L. lactis, seven and three compounds, which inhibit the transport activity more than the lead compound Zosuquidar, were found. Interestingly, transport inhibition for LmrCD was very specific, with a drastic reduction by one compound while its diastereomers showed hardly an effect. Thus, the present study reveals new potent inhibitors for the ABC-type MDR efflux pumps studied with the inhibitors of Pdr5 and LmrCD being of particular interest as these proteins are well known model systems for their homologs in pathogenic fungi and Gram-positive bacteria.

Description

Zosuquidar (LY335979) is a potent negative modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM.

Keywords:

Zosuquidar,167354-41-8,LY335979,Natural Products,P-gp, buy Zosuquidar , Zosuquidar supplier , purchase Zosuquidar , Zosuquidar cost , Zosuquidar manufacturer , order Zosuquidar , high purity Zosuquidar

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: