Zosuquidar |
| Catalog No.GC16672 |
A modulator of P-gp
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 167354-41-8
Sample solution is provided at 25 µL, 10mM.
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Zosuquidar (LY335979) 3HCl is a novel and potent modulator of P-glycoprotein (P-gp) [1]. P-gp is wildly expressed in brain, liver, small intestine and tumor cells and acts as an efflux pump responsible for multidrug resistance in tumor cells. Overexpression of Pgp in tumors results in multidrug resistance (MDR) to structurally unrelated oncolytics [2].
In vitro: In CEM/VLB100 cells, LY335979 treatment (0.1 μM) fully restored the sensitivity to vinblastine, doxorubicin (Dox), etoposide, and Taxol. In CEM/VLB100 plasma membranes, LY335979 blocked [3H]azidopinephotoaffinity labeling of the M(r) approximately 170,000 Pgp and competitively inhibited equilibrium binding of [3H]vinblastine to Pgp with the Ki value of approximately 0.06 μM [3]. In all P-gp-expressing leukemia cell linesincluding K562/HHT40, K562/HHT90, K562/DOX and HL60/DNR, Zosuquidar completely or partially restored drug sensitivity. In primary AML blasts with active P-gp, Zosuquidar enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumabozogamicin (Mylotarg)[4].
In vivo: In mice bearing P388/ADR murine leukemia cells,treatment with LY335979 in combination with Dox or etoposide significantly increased in life span with no apparent alteration of pharmacokinetics. In a MDR human non-small cell lung carcinoma nude mouse xenograft model, LY335979 enhanced the antitumor activity of Taxol [3].
Clinical trials: In patients with untreated non-Hodgkin's lymphoma,a phase I/II trial was conducted to investigate the safety and tolerance of zosuquidar. In patients giving three doses of 500 mg of zosuquidar p.o. in combination with CHOX, toxicity was minimal and no enhancement of CHOP-related toxicity was observed [5]. In patients with advanced solid tumours in Phase I study, zosuquidar(100–300 mg/m2) can inhibit vinorelbine clearance to a modest degree[6].
References:
[1] Cripe L D, Uno H, Paietta E M, 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[J]. Blood, 2010, 116(20): 4077-4085.
[2] Chaudhary P M, Roninson I B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells[J]. Cell, 1991, 66(1): 85-94.
[3] Dantzig A H, Shepard R L, Cao J, et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979[J]. Cancer Research, 1996, 56(18): 4171-4179.
[3] Tang R, Faussat A M, Perrot J Y, et al. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML)[J]. BMC cancer, 2008, 8(1): 1.
[4] Morschhauser F, Zinzani P L, Burgess M, et al. Phase I/II trial of a P-glycoprotein inhibitor, Zosuquidar. 3HCl trihydrochloride (LY335979), given orally in combination with the CHOP regimen in patients with non-Hodgkin's lymphoma[J]. Leukemia & lymphoma, 2007, 48(4): 708-715.
[5] Lê L H, Moore M J, Siu L L, et al. Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours[J]. Cancer chemotherapy and pharmacology, 2005, 56(2): 154-160.
| Cas No. | 167354-41-8 | SDF | |
| Chemical Name | (2R)-1-(4-((1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c][7]annulen-6-yl)piperazin-1-yl)-3-(quinolin-5-yloxy)propan-2-ol | ||
| Canonical SMILES | FC1([C@@](C2=C([H])C([H])=C([H])C([H])=C23)([H])[C@]1([H])C4=C([H])C([H])=C([H])C([H])=C4C3([H])N5C([H])([H])C([H])([H])N(C([H])([H])[C@@](C([H])([H])OC6=C([H])C([H])=C([H])C7=C6C([H])=C([H])C([H])=N7)([H])O[H])C([H])([H])C5([H])[H])F | ||
| Formula | C32H31F2N3O2 | M.Wt | 527.6 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8954 mL | 9.4769 mL | 18.9538 mL |
| 5 mM | 0.3791 mL | 1.8954 mL | 3.7908 mL |
| 10 mM | 0.1895 mL | 0.9477 mL | 1.8954 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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