ChemicalBook CAS DataBase List 182959-28-0

182959-28-0

Name	YM-53601 free base
CAS	182959-28-0
Molecular Formula	C21H21FN2O
MDL Number	MFCD00951376
Molecular Weight	336.4
MOL File	182959-28-0.mol

Chemical Properties

Boiling point	541.2±40.0 °C(Predicted)
density	1.30±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	Soluble in DMSO
pka	16.62±0.30(Predicted)

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H302-H315-H319-H335
Precautionary statements	P261-P305+P351+P338

Hazard Information

Uses

YM-53601 free base, a squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in vivo[1]. YM-53601 free base inhibits squalene synthase derived from human hepatoma cells with an IC50 of 79 nM. Lipid-lowering agent[2]. YM-53601 free base is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) enzyme activity and abrogates HCV propagation[3].

in vivo

YM-53601 free base suppresses cholesterol biosynthesis in rats (ED₅₀, 32 mg/kg)^[1].
YM-53601 free base also reduces plasma non-HDL cholesterol levels in hamsters by approximately 70% at an oral dose of 50 mg/kg/day for 5 days^[2].
YM-53601 free base potentiates Doxorubicin-mediated hepatocellular carcinoma cells (HCC) growth arrest and cell death in vivo^[4]. "

Animal Model:	Sprague-Dawley (SD) rats weighing 150-170?g^[1]
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^[4]
Dosage:	15 mg/kg
Administration:	2 wk of daily treatment by p.o. gavage
Result:	Significantly decreased the intratumor cholesterol levels.

References

[1] T Ugawa,?et al. YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species. Br J Pharmacol.?2000 Sep;131(1):63-70. DOI:10.1038/sj.bjp.0703545
[2] Tsukasa Ishihara, et al. Syntheses of 3-ethylidenequinuclidine derivatives as squalene synthase inhibitors. Part 2: enzyme inhibition and effects on plasma lipid levels. Bioorg Med Chem.?2003 Aug 15;11(17):3735-45. DOI:10.1016/s0968-0896(03)00336-5
[3] Eun-Mee Park,?et al. Farnesyl-diphosphate farnesyltransferase 1 regulates hepatitis C virus propagation. FEBS Lett.?2014 May 2;588(9):1813-20. DOI:10.1016/j.febslet.2014.03.043
[4] Joan Montero,et al.Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma. Cancer Res.?2008 Jul 1;68(13):5246-56. DOI:10.1158/0008-5472.CAN-07-6161

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