zosuquidar

Zosuquidar is an experimental small molecule antineoplastic agent that acts as a potent and selective inhibitor of P-glycoprotein (ABCB1/MDR1), a transmembrane efflux pump responsible for multidrug resistance in cancer cells[2][3][9]. By inhibiting P-glycoprotein-mediated drug efflux from tumor cells—particularly those overexpressing this transporter—zosuquidar restores sensitivity to chemotherapeutic agents that would otherwise be expelled from the cell before exerting their cytotoxic effects[2][5]. It is a difluorocyclopropyl quinoline derivative with high affinity for its target and has been investigated primarily in acute myeloid leukemia (AML) and myelodysplastic syndrome[8][9]. The compound was originally discovered by Syntex Corporation (later acquired by Roche), then licensed to Eli Lilly for further development[3][9]. Despite reaching phase III clinical trials and receiving orphan drug status from the FDA for AML in 2006[9], development was discontinued after pivotal studies failed to demonstrate significant clinical benefit over standard therapy[7].

Other names

zosuquidarzosuquidarumZosuquidar [INN]ZOSUQUIDAR [MI]ZOSUQUIDAR [WHO-DD]1-Piperazineethanol, 4-((1aalpha,6alpha,10balpha)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo(a,e)cyclopropa(c)cycloheptan-6-yl)-alpha-1((5-quinolinyloxy)methyl-, (alphaR)-(2R)-1-(4-((2R,4S,11R)-3,3-difluorotetracyclo(10.4.0.0^(2,4).0^(5,10))hexadeca-1(16),5,7 ,9 ,12 ,14-hexaen -11 -yl)piperazin -1 -yl ) -3 -(quinolin -5-yloxy )propan -2 -ol(2R)-1-{4-[ (2R ,4S ,11 R ) -3 ,3-difluorotetracyclo[10 .4 .0 .0^{2 ,4} .0^{5 ,10}]hexadeca – 1(16), 5 ,7 ,9 ,12 ,14-hexaen – 11 – yl ]piperazin – 1 – yl }–3–(quinolin–5-yloxy)propan–2–ol