[CAS NO. 182959-33-7] YM-53601
PRODUCTS SPECIFICATIONS [182959-33-7]
DESCRIPTION [182959-33-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 372.86 |
| Molecular Formula | C21H22ClFN2O |
| SMILES | F/C(COC1=CC(NC2=C3C=CC=C2)=C3C=C1)=C4CN5CCC/4CC5.[H]Cl |
Summary
YM-53601, a squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in vivo [1] . YM-53601 inhibits squalene synthase derived from human hepatoma cells with an IC 50 of 79 nM. Lipid-lowering agent [2] . YM-53601 is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 ( FDFT1 ) enzyme activity and abrogates HCV propagation [3] .
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 IC
50
s of 90, 170, 46, 45, and 79 nM, respectively
[1]
.
YM-53601 inhibits conversion of [3H]farnesyl diphosphate to [
3
H]squalene by hamster liver squalene synthase with the IC
50
of 170 nM
[2]
.
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
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [4]
| 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 (ED
50
, 32 mg/kg)
[1]
.
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
[2]
.
YM-53601 potentiates Doxorubicin-mediated hepatocellular carcinoma cells (HCC) growth arrest and cell death in vivo
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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 ED 50 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 268.20 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6820 mL | 13.4099 mL | 26.8197 mL |
| 5 mM | 0.5364 mL | 2.6820 mL | 5.3639 mL |
| 10 mM | 0.2682 mL | 1.3410 mL | 2.6820 mL |
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.
- [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.
- [3] Eun-Mee Park, et al. Farnesyl-diphosphate farnesyltransferase 1 regulates hepatitis C virus propagation. FEBS Lett. 2014 May 2;588(9):1813-20.
- [4] Joan Montero,et al.Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma. Cancer Res. 2008 Jul 1;68(13):5246-56.