| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Triparanol targets DHCR24 (3β-hydroxysterol-Δ24-reductase), the enzyme that catalyzes the conversion of desmosterol to cholesterol in the final step of the cholesterol biosynthesis pathway. It acts as a potent inhibitor with a Ki of 0.523 µM. By inhibiting DHCR24, triparanol leads to the accumulation of desmosterol and a decrease in cellular cholesterol levels. This disruption of cholesterol homeostasis affects various cellular processes, including membrane fluidity, lipid raft formation, and cell signaling. Triparanol can also interfere with the post-translational modification of Hedgehog signaling molecules and the sterol sensing domain of its receptor PTCH1, leading to the downregulation of Hedgehog signaling. It has also been described as an inhibitor of melanin-concentrating hormone receptor 1 (MCHR1).
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| ln Vitro |
Triparametric alcohols have the ability to halt the growth and trigger apoptosis in a range of human cancer cells, such as those found in the lung, breast, liver, pancreatic, prostate, and melanoma [2]. The growth inhibition can be restored by adding cholesterol exogenously.
In vitro, triparanol has been shown to inhibit cholesterol biosynthesis in cultured cells, including hepatocytes, fibroblasts, and cancer cells. Treatment of cells with the compound leads to a reduction in cholesterol synthesis and an accumulation of desmosterol. Triparanol can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer, and melanoma cells. Growth inhibition can be rescued by the exogenous addition of cholesterol. The compound's ability to inhibit DHCR24 has been confirmed in enzymatic assays using purified enzyme preparations. In addition to its effects on cholesterol metabolism, triparanol has been shown to regulate Iks channel function. |
| ln Vivo |
In vivo, triparanol has been studied for its cholesterol-lowering effects in subjects with and without coronary artery disease. It was the first major drug used clinically to lower cholesterol levels. However, its clinical use was discontinued due to adverse reactions, notably causing cataracts. The compound has also been investigated for its anti-tumor activity, as cancer cells often have altered cholesterol metabolism and may be more susceptible to cholesterol depletion. Triparanol suppresses human tumor growth in preclinical models.
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| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for triparanol involve measuring its inhibition of DHCR24 enzymatic activity. The assay uses a microsomal preparation containing DHCR24 or a purified recombinant enzyme and a substrate, such as desmosterol, in the presence of NADPH. The conversion of desmosterol to cholesterol is measured using gas chromatography-mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC). The compound is incubated with the enzyme and substrate at varying concentrations, and the IC50 or Ki is determined. For triparanol, a Ki of 0.523 µM has been reported. Radioligand binding assays can also be performed to study its interaction with other targets, such as MCHR1.
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| Cell Assay |
In vitro cell-based assays for triparanol are performed using various cell lines, such as hepatocytes, fibroblasts, or cancer cells. Cells are treated with the compound, and the effects on cholesterol synthesis, cholesterol levels, and desmosterol accumulation are measured. Radiolabeled acetate or mevalonate can be used to trace cholesterol synthesis. The compound's effects on cell proliferation, apoptosis, and signaling pathways are also assessed. These assays are used to study the cellular consequences of DHCR24 inhibition and cholesterol depletion, as well as the compound's anti-tumor activity.
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| Animal Protocol |
In vivo animal experiments for triparanol are conducted using rodent models to study its effects on cholesterol metabolism, tumor growth, and other physiological processes. The compound is administered orally or intraperitoneally. Cholesterol levels in plasma and tissues are measured. Tumor growth is assessed in xenograft models. The compound's effects on gene expression and signaling pathways are analyzed in tissue samples. These studies help to understand the role of cholesterol in various diseases and the potential of DHCR24 as a therapeutic target.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of triparanol have been characterized in preclinical studies. The compound has a molecular weight of 438.01 and a molecular formula of C27H32ClNO2. It appears as a white to light yellow solid powder with a melting point of 102.9-103.7°C. The compound has a LogP of 5.847, indicating high lipophilicity. Powder is stable when stored at -20°C for 3 years or at 4°C for 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. The compound is typically administered orally. Specific PK parameters, such as half-life and bioavailability, are determined in animal studies via LC-MS/MS analysis of plasma samples.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for triparanol are significant, as the compound was associated with serious adverse effects. It was found to cause cataracts and skin abnormalities in clinical trials, leading to its withdrawal from the market in 1962. These side effects are attributed to the accumulation of desmosterol in tissues, which disrupts normal cellular function, particularly in the lens of the eye and the skin. The compound's toxicological profile highlights the importance of desmosterol and cholesterol homeostasis for normal physiology. It is also known to cause calcium increase in mouse skeletal muscles, inducing myotonic dystrophy-like clinical manifestations.
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| References | |
| Additional Infomation |
Tripalprazole is a stilbene compound with anti-coronavirus activity. It is a lipid-lowering drug, but it has high ocular toxicity. According to the 11th edition of the Merck Index, the compound was withdrawn from the market in 1962 due to its association with the formation of irreversible cataracts.
Other information: Triparanol is a historical compound that was developed as a cholesterol-lowering drug but was withdrawn due to side effects. It is now used as a research tool to study cholesterol metabolism and the function of DHCR24. The compound is also known as MER-29 and NSC-65345. Its CAS number is 78-41-1. It is available from chemical suppliers for preclinical research purposes. The compound is for research use only and not for human use. |
| Molecular Formula |
C27H32CLNO2
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|---|---|
| Molecular Weight |
438.01
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| Exact Mass |
437.212
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| CAS # |
78-41-1
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| PubChem CID |
6536
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| Appearance |
White to light yellow solid powder
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| Density |
1.133g/cm3
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| Boiling Point |
546.9ºC at 760 mmHg
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| Melting Point |
102.9-103.7ºC
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| Flash Point |
284.5ºC
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| Index of Refraction |
1.582
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| LogP |
5.847
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
31
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| Complexity |
490
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SYHDSBBKRLVLFF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H32ClNO2/c1-4-29(5-2)18-19-31-26-16-12-24(13-17-26)27(30,23-10-6-21(3)7-11-23)20-22-8-14-25(28)15-9-22/h6-17,30H,4-5,18-20H2,1-3H3
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| Chemical Name |
2-(4-chlorophenyl)-1-[4-[2-(diethylamino)ethoxy]phenyl]-1-(4-methylphenyl)ethanol
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| Synonyms |
NSC-65345; NSC 65345; Triparanol
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2831 mL | 11.4153 mL | 22.8305 mL | |
| 5 mM | 0.4566 mL | 2.2831 mL | 4.5661 mL | |
| 10 mM | 0.2283 mL | 1.1415 mL | 2.2831 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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