[CAS NO. 167465-36-3] Zosuquidartrihydrochloride
PRODUCTS SPECIFICATIONS [167465-36-3]
DESCRIPTION [167465-36-3]
Overview
| MDL | MFCD00942300 |
|---|---|
| Molecular Weight | 636.99 |
| Molecular Formula | C32H34Cl3F2N3O2 |
| SMILES | FC1([C@H]2[C@@H]1C3=C([C@@H](C4=CC=CC=C42)N5CCN(CC5)C[C@H](COC6=C7C=CC=NC7=CC=C6)O)C=CC=C3)F.Cl.Cl.Cl |
14 Publications Citing Use of MCE
- [1]Cancer Cell. 2017 Apr 10;31(4):501-515.e8.
- [2]Blood Adv. 2020 Oct 27;4(20):5062-5077.
- [3]Crit Rev Anal Chem. 2021 Mar 10;1-15.
- [4]Biomed Pharmacother. 2020 Sep;129:110506.
- [5]Pharmaceutics. 2021, 13(4), 559.
- [6]Antiviral Res. 2021 Jun 28;105124.
- [7]Viruses. 2020 Aug 17;12(8):901.
- [8]Drug Metab Dispos. 2017 May;45(5):449-456.
- [9]J Pharm Biomed Anal. 2012 Jul;66:232-9.
- [10]J Chromatogr B Analyt Technol Biomed Life Sci. 2018 May 31;1092:72-81.
- [11]Biochem Biophys Res Commun. 2021 May.
- [12]Biomed Res Int. 2020 Nov 29;2020:8878158.
- [13]Biomed Res Int. 2014;2014:850493.
- [14]Exp Ther Med. 2020 Dec 7.
Summary
Zosuquidar (LY335979) trihydrochloride is a P-glycoprotein (P-gp) inhibitor ( K i =59 nM). Zosuquidar trihydrochloride shows anti-tumor activities, and can be used in acute myelogenous leukemia (AML) research [1] [2] [3] .
IC50 & Target
Ki: 59nM (P-glycoprotein) [1] .
In Vitro
Zosuquidar (0.3 μM; 48 h) enhances the cytotoxicity of DNR (substrates for P-glycoproteins) in P-glycoproteins active cell lines
[2]
.
Zosuquidar (5-16 μM; 72 h) treatment alone shows high cytotoxic concentration to drug-sensitive and MDR cell lines
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay [2]
| Cell Line: | K562 and HL60 cells |
| Concentration: | 0.3 μM |
| Incubation Time: | 48 hours |
| Result: | Enhanced the cytotoxicity of DNR (substrates for P-glycoproteins) in K562/DOX cells more than 45.5-fold. |
Cell Cytotoxicity Assay [1]
| Cell Line: | CCRF-CEM, CEM/VLB100, P388, P388/ADR, MCF7, MCF7/ADR, 2780, 2780AD, UCLA-P3, UCLA-P3.003VLB cells |
| Concentration: | 5-16 μM |
| Incubation Time: | 72 hours |
| Result: | Showed IC 50 s of 6, 7, 15, 8, 7, 15, 11, 16, >5, >5 μM for CCRF-CEM, CEM/VLB100, P388, P388/ADR, MCF7, MCF7/ADR, 2780, 2780AD, UCLA-P3, UCLA-P3.003VLB cells, respectively. |
In Vivo
Zosuquidar (intraperitoneal injection; 30, 10, 3, or 1 mg/kg; once daily; 5 d) treatment shows a significant increase in life span
[1]
.
Zosuquidar (intraperitoneal injection; 30 mg/kg; once daily; 5 d) treatment shows the potentiation with a combined of Doxorubicin
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Mice implanted with P388/ADR tumors [1] |
| Dosage: | 30, 10, 3, or 1 mg/kg |
| Administration: | Intraperitoneal injection; 30, 10, 3, or 1 mg/kg; once daily; 5 days |
| Result: | Exihibited a significantly increased survival compared to the group treated with Doxorubicin alone (P<0.001). |
| Animal Model: | Mice implanted with P388 or P388/ADR murine leukemia cells [1] |
| Dosage: | 30 mg/kg |
| Administration: | Intraperitoneal injection; 30 mg/kg; once daily; 5 days |
| Result: | Observed significant antitumor activity against the MDR P388/ADR cell lines when mice were treated with a combined dose of 30 mg/kg LY335979 and 1 mg/kg Doxorubicin (P=0.1). |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00233909 | Kanisa Pharmaceuticals |
Leukemia, Myeloid
|
October 2005 | Phase 1|Phase 2 |
| NCT00046930 | Eastern Cooperative Oncology Group|National Cancer Institute (NCI)|Eli Lilly and Company|Kanisa Pharmaceuticals |
Leukemia|Myelodysplastic Syndromes
|
July 2002 | Phase 3 |
| NCT00129168 | Kanisa Pharmaceuticals |
Leukemia, Myeloid
|
August 2005 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* The compound is unstable in solutions, freshly prepared is recommended.
Solvent & Solubility
H 2 O : 5 mg/mL ( 7.85 mM ; Need ultrasonic)
DMSO : 1 mg/mL ( 1.57 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5699 mL | 7.8494 mL | 15.6988 mL |
| 5 mM | 0.3140 mL | 1.5699 mL | 3.1398 mL |
| 10 mM | --- | --- | --- |
-
1.
Zosuquidar is dissolved in 20% ethanol-saline [5] .
References
- [1] A H Dantzig, 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] Ruoping Tang, et al. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML). BMC Cancer. 2008 Feb 13;8:51.
- [3] Larry D Cripe, 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
