| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
ACAT1/ACAT2 (acyl-CoA:cholesterol acyltransferase)
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|---|---|
| ln Vitro |
In the presence of acLDL without Cu2+, foam cells collected esterified cholesterol (EC) over 24 hours, a process that is inhibited by KY-455 and YM-750[3].
In vitro, YM-750 potently inhibits ACAT with an IC50 of 0.18 uM. In foam cell assays, in the presence of acLDL without Cu2+, esterified cholesterol accumulates in cells over 24 hours, a process that is suppressed by YM-750. Treatment with YM-750 significantly decreases cholesteryl ester levels in cultured cells, affirming its role as an effective ACAT inhibitor. YM-750 inhibits the conversion of cholesterol and long-chain fatty-acyl-coenzyme A into cholesteryl esters. |
| ln Vivo |
YM-750 exhibits hypocholesterolemic and antiatherosclerotic activity in vivo, as demonstrated in animal models. ACAT inhibition by YM-750 leads to a decrease in the formation of cholesteryl esters, resulting in reduced serum cholesterol levels and inhibition of atherosclerotic plaque progression. It was developed for the treatment of hyperlipidemia and advanced to Phase 1 clinical trials before being discontinued.
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| Enzyme Assay |
Recombinant human ACAT is expressed in insect cells (Sf9) or CHO cells, and microsomal fractions are prepared. The enzyme activity is measured using [14C]-oleoyl-CoA as the acyl donor and cholesterol as the acceptor in a reaction buffer containing potassium phosphate (pH 7.4), BSA, and dithiothreitol. Reactions are incubated at 37degC for 10-30 minutes, stopped by organic extraction (chloroform/methanol), and the product (cholesteryl oleate) is separated by TLC and quantified by radiometric detection or liquid scintillation counting. IC50 values are determined from dose-response curves.
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| Cell Assay |
Murine J774 macrophages or THP-1-derived macrophages are cultured in RPMI-1640 with 10% FBS. Cells are treated with YM-750 (0.01-10 uM) for 24-48 hours in the presence of acetylated LDL (acLDL, 50 ug/mL) to induce foam cell formation. Esterified cholesterol accumulation is quantified by enzymatic colorimetric kits after lipid extraction with hexane/isopropanol. Cellular cholesterol esterification is also assessed by [14C]-oleate incorporation into cholesteryl esters. Foam cell formation is visualized by Oil Red O staining.
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| Animal Protocol |
YM-750 was evaluated in animal models of hyperlipidemia and atherosclerosis. Typical protocols involve feeding hamsters or rabbits a high-cholesterol diet for 4-8 weeks to induce hypercholesterolemia and aortic fatty streak formation. YM-750 is administered orally (gavage) at doses of 1-30 mg/kg daily for 4-12 weeks. Endpoints include plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (by enzymatic assays), and aortic fatty streak area (by en face Oil Red O staining or histomorphometry).
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data reported for YM-750. Based on chemical similarity to other ACAT inhibitors, it is expected to be orally bioavailable with absorption from the gastrointestinal tract. Metabolism likely occurs in the liver via phase I (CYP450) and phase II (glucuronidation) enzymes. Excretion is primarily via bile and urine. Plasma half-life and protein binding are not publicly available.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for YM-750. As an ACAT inhibitor, it may influence cellular lipid homeostasis across various tissues. Preclinical studies likely established a safety profile supporting its advancement to Phase 1 clinical trials. However, specific adverse effects and toxicological findings are not publicly available. The compound was discontinued in Phase 1, possibly due to efficacy or tolerability issues.
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| References |
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| Additional Infomation |
YM-750 (also known as YM 750) is a small molecule ACAT inhibitor developed by Yamanouchi Pharmaceutical Co., Ltd. for the treatment of hyperlipidemia. The compound advanced to Phase 1 clinical trials but was discontinued. It is not approved for clinical use. ACAT inhibition leads to reduced cholesteryl ester formation, decreased foam cell formation, altered cellular lipid homeostasis, modulated lipoprotein profiles, and inhibited atherosclerotic plaque progression. YM-750 is a research tool for studying ACAT biology and cholesterol metabolism.
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| Molecular Formula |
C31H36N2O
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|---|---|
| Molecular Weight |
452.63
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| Exact Mass |
452.283
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| CAS # |
138046-43-2
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| PubChem CID |
9911716
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| Appearance |
White to off-white solid powder
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| LogP |
7.953
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
658
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C(=C1)C)NC(=O)N(CC2=CC3=C(C=C2)C4=CC=CC=C4C3)C5CCCCCC5)C
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| InChi Key |
FMLJREWZCZHGGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H36N2O/c1-21-16-22(2)30(23(3)17-21)32-31(34)33(27-11-6-4-5-7-12-27)20-24-14-15-29-26(18-24)19-25-10-8-9-13-28(25)29/h8-10,13-18,27H,4-7,11-12,19-20H2,1-3H3,(H,32,34)
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| Chemical Name |
1-cycloheptyl-1-(9H-fluoren-2-ylmethyl)-3-(2,4,6-trimethylphenyl)urea
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (220.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2093 mL | 11.0466 mL | 22.0931 mL | |
| 5 mM | 0.4419 mL | 2.2093 mL | 4.4186 mL | |
| 10 mM | 0.2209 mL | 1.1047 mL | 2.2093 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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