LY335979 (Zosuquidar 3HCl)

Cas No.:	167465-36-3
Chemical Name:	Zosuquidar Trihydrochloride
Synonyms:	Zosuquidar trihydrochloride;LY335979;Zosuquidar (LY335979) 3HCl;Zosuquidar 3HCl;Zosuquidar Trihydroc;ZOSUQUIDAR TRIHYSROCHLORIDE;LY-335979 trihydrochloride;RS 33295-198 trihydrochloride;RS-33295-198, ZOSUQUIDAR;RS 33295-198;(2R)-1-{4-[(1aR,6r,10bS)-1,1-Difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]piperazin-1-yl}-3-(quinolin-5-yloxy)propan-2-ol trihydrochloride;Trihydrochloride;LY335979, RS 33295-198;Zosuquidr.3HCl(LY335979);LY335979 (Zosuquidar 3HCl);RS 33295-198 (D06387) 3HCl;Zosuquidar HCl;LY 335979;Zosuquidar (trihydrochloride);LY335979 trihydrochloride;Zosuquidar trihydrochloride (USAN);Zosuquidar Trihydrochloride [USAN];813AGY3126;DSSTox_CID_31451;DSSTox_RID_97337;DSSTox_GSID_57662;C32H34Cl3F2N3O2;RS 3329
SMILES:	Cl.Cl.Cl.O[C@@H](COC1C2C(=NC=CC=2)C=CC=1)CN3CCN(CC3)C4C5=C(C=CC=C5)[C@H]6C(F)(F)[C@H]6C7=C4C=CC=C7
Formula:	C32H34Cl3F2N3O2
M.Wt:	636.9871
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Zosuquidar trihydrochloride is an inhibitor of P-glycoprotein with a Ki value of 59 nM.
In Vivo:	Zosuquidar trihydrochloride is only moderately active as an inhibitor of P-gp at the blood-brain. An oral dose of 25 mg/kg of zosuquidar trihydrochloride increases the brain concentrations by about 2.5-fold at 1 h and 5-fold at 24 h after paclitaxel administrationbarrier[3]. Zosuquidar enhances the brain uptake of nelfinavir in a dose-dependent manner. Brain tissue/plasma nelfinavir concentration ratios increase from 0.06±0.03 in the absence of zosuquidar administration and 0.09±0.02 between 2 and 6 h after a 2 mg/kg intravenous dose of zosuquidar to 0.85±0.19 after 6h and 1.58±0.67 after 20 mg/kg zosuquidar[4].
In Vitro:	Zosuquidar completely or partially restores drug sensitivity in all P-gp-expressing leukemia cell lines and enhances the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AmL blasts with active P-gp. In addition, P-gp inhibition by zosuquidar is found to be more potent than cyclosporine A in cells with highly active P-gp[2].