YM-53601

YM-53601 is an inhibitor of squalene synthase activity that acts by lowering cholesterol as well as triglycerides. YM-53601, a squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in vivo. YM-53601 inhibits squalene synthase derived from human hepatoma cells with an IC50 of 79 nM. Lipid-lowering agent. YM-53601 is also an inhibitor of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) enzyme activity and abrogates HCV propagation.

Product information

CAS Number: 182959-33-7

Molecular Weight: 372.86

Formula: C21H22ClFN2O

Chemical Name: 2-{2-[(3E)-1-azabicyclo[2.2.2]octan-3-ylidene]-2-fluoroethoxy}-9H-carbazole hydrochloride

Smiles: Cl.F/C(/COC1=CC2NC3=CC=CC=C3C=2C=C1)=C1/CN2CCC/1CC2

InChiKey: JWXYVHMBPISIJQ-TVWXOORISA-N

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-;

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

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.

References:

1. Ugawa T, Kakuta H, Moritani H, Inagaki O, Shikama H. YM-53601, a novel squalene synthase inhibitor, suppresses lipogenic biosynthesis and lipid secretion in rodents. Br J Pharmacol. 2003 May;139(1):140-6. PubMed PMID: 12746232; PubMed Central PMCID: PMC1573827.
2. Ishihara T, Kakuta H, Moritani H, Ugawa T, Sakamoto S, Tsukamoto Si, Yanagisawa I. 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. PubMed PMID: 12901918.

Products are for research use only. Not for human use.