Zosuquidar

Names

[ Name ]:
Zosuquidar

[Synonym ]:
(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
Unii-ab5K82X98y
(2R)-1-{4-[(1aR,10bS)-1,1-Difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c][7]annulen-6-yl]-1-piperazinyl}-3-(5-quinolinyloxy)-2-propanol
Zosuquidar
Zosuquidar [inn]
1-Piperazineethanol, 4-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]-α-[(5-quinolinyloxy)methyl]-, (αR)-

Biological Activity

[Description]:

Zosuquidar (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-glycoproteinZosuquidar (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.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

Research Areas >> Cancer

[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.

[Related Small Molecules]