YM-53601

Category	Hepatitis C Virus (HCV)
CAS	182959-33-7
Description	YM-53601 is a squalene synthase inhibitor with IC50s of 79 and 90 nM in HepG2 cells and rat liver microsomes, respectively. It is a lipid lowering agent that can reduce plasma cholesterol and triglyceride levels in vivo and inhibit cholesterol biosynthesis in rats (ED50 = 32 mg/kg). It is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) enzyme activity and can inhibit the proliferation of HCV.

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Product Information

Synonyms	9H-Carbazole, 2-[(2E)-2-(1-azabicyclo[2.2.2]oct-3-ylidene)-2-fluoroethoxy]-, hydrochloride (1:1); (E)-3-[2-(Carbazol-2-yloxy)-1-fluoroethylidene]quinuclidine hydrochloride; 2-[(2E)-2-(1-azabicyclo[2.2.2]oct-3-ylidene)-2-fluoroethoxy]-9H-carbazole, monohydrochloride
IUPAC Name	2-[(2E)-2-(1-azabicyclo[2.2.2]octan-3-ylidene)-2-fluoroethoxy]-9H-carbazole;hydrochloride
Molecular Weight	372.86
Molecular Formula	C21H21FN2O.HCl
Canonical SMILES	C1CN2CCC1C(=C(COC3=CC4=C(C=C3)C5=CC=CC=C5N4)F)C2.Cl
InChI	InChI=1S/C21H21FN2O.ClH/c22-19(18-12-24-9-7-14(18)8-10-24)13-25-15-5-6-17-16-3-1-2-4-20(16)23-21(17)11-15;/h1-6,11,14,23H,7-10,12-13H2;1H/b19-18-;
InChIKey	JWXYVHMBPISIJQ-TVWXOORISA-N
Melting Point	236.5-237.2°C
Purity	≥98%
Solubility	Soluble in DMF, DMSO, Ethanol
Appearance	Crystalline Solid
Storage	Store at -20°C
Complexity	528
Exact Mass	372.1404692
In Vitro	YM-53601 inhibits squalene synthase activities in hepatic microsomes from several species of rat, hamster, guinea-pig, rhesus monkey, and human-derived HepG2 cell with IC50s of 90, 170, 46, 45, and 79 nM, respectively. YM-53601 inhibits conversion of [3H]farnesyl diphosphate to [3H]squalene by hamster liver squalene synthase with the IC50 of 170 nM. YM-53601 (1 μM) potentiates the susceptibility of H35 cells to thapsigargin, lonidamine, and doxorubicin. YM-53601 (1 μM) reduces the mitochondrial cholesterol levels in both H35 and HepG2 cells. Cell Viability Assay Cell Line: H35 and HepG2 cells Concentration: 1 μM Incubation Time: 24 hours Result: Reduced the mitochondrial cholesterol levels in both H35 and HepG2 cells.
In Vivo	YM-53601 suppresses cholesterol biosynthesis in rats (ED50, 32 mg/kg). YM-53601 also reduces plasma non-HDL cholesterol levels in hamsters by approximately 70% at an oral dose of 50 mg/kg/day for 5 days. YM-53601 potentiates Doxorubicin-mediated hepatocellular carcinoma cells (HCC) growth arrest and cell death in vivo. Animal Model: Sprague-Dawley (SD) rats weighing 150-170 g Dosage: 6.25, 12.5, 25 or 50 mg/kg Administration: Given a single p.o. Result: Inhibited cholesterol biosynthesis from acetate in a dose-dependent manner in rats. The ED50 value for YM-53601 cholesterol biosynthesis inhibition is 32 mg/kg. Animal Model: Five- to six-week-old male BALB/c athymic (nu/nu) nude mice Dosage: 15 mg/kg Administration: 2 wk of daily treatment by p.o. gavage Result: Significantly decreased the intratumor cholesterol levels.
PSA	28.26000
Target	Farnesyl Transferase; HCV