| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Liarozole primarily targets the cytochrome P450 enzyme CYP26, which is responsible for the catabolism of retinoic acid. By inhibiting CYP26, it blocks the 4-hydroxylation of retinoic acid. This inhibition leads to an increase in the concentration of endogenous all-trans-retinoic acid (ATRA). ATRA is a potent signaling molecule that regulates gene expression involved in cell growth, differentiation, and apoptosis. Liarozole also inhibits aromatase, an enzyme that converts androgens to estrogens.
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| ln Vitro |
Cell growth in MCF-7 cells is inhibited by rizazole (0.01~10 μM; 9 days) [3]. Chondrogenesis in mesenchymal cells is totally inhibited by liarozole (1 μM; 4 days) [4].
In vitro, liarozole inhibits the cytochrome P450 (CYP26)-dependent 4-hydroxylation of retinoic acid with an IC50 of 7 μM. This inhibition results in an increase in endogenous ATRA levels. The increased ATRA then inhibits cell proliferation and induces cell differentiation in various cell lines. Its ability to inhibit both retinoic acid metabolism and aromatase makes it a multi-targeted compound with potential anticancer activity. |
| ln Vivo |
Estrogen-stimulated vaginal keratosis is reversed by rizazone (5–20 mg/kg; oral; 3 days) [5]. The tumor burden is greatly reduced by rizazol (40 mg/kg; oral; 21 days) [6].
In vivo, liarozole is an orally active agent. By inhibiting CYP26, it increases tissue levels of retinoic acid. This increase in retinoic acid leads to the inhibition of cell proliferation and induction of cell differentiation, which are the basis for its potential antitumor effects. It has been studied for its potential in treating cancers, including prostate, breast, and ovarian cancer. |
| Enzyme Assay |
Non-cell-based enzyme assays for liarozole typically involve the use of liver microsomes or recombinant CYP26 enzymes. The enzyme is incubated with its substrate, retinoic acid, and NADPH. Liarozole is added at various concentrations, and the production of 4-hydroxy-retinoic acid, the primary metabolite, is measured using HPLC or LC-MS/MS. An IC50 value is determined from a dose-response curve.
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| Cell Assay |
Cell proliferation experiment [3]
Cell Types: MCF-7 cell Tested Concentrations: 0.01~10 μM Incubation Duration: 9 days Experimental Results: 35% inhibitory effect on cell proliferation at 10 μM. Cell differentiation analysis[4] Cell Types: Mesenchymal cells Tested Concentrations: 1 μM Incubation Duration: 4 days Experimental Results: Complete inhibition of chondrogenesis. Cellular assays for liarozole are performed using cancer cell lines that are sensitive to retinoic acid. The cells are treated with liarozole at various concentrations, and the levels of retinoic acid in the cells are measured. The compound's ability to increase retinoic acid levels is quantified. The effects on cell proliferation and differentiation are then assessed using standard assays such as MTT or by measuring the expression of differentiation markers. |
| Animal Protocol |
Animal/Disease Models: ovariectomized rats [5]
Doses: 5~20 mg/kg Route of Administration: Po; 3-day Experimental Results: Reverse vaginal keratinization caused by estrogen stimulation. Animal/Disease Models: SCID (severe combined immunodeficient) mouse [6] Doses: 40 mg/kg Route of Administration: Po; 21-day Experimental Results: Inhibition of tumor growth and survival. In vivo animal models for liarozole would typically involve xenograft studies in immunodeficient mice. Mice bearing human cancer xenografts are treated with liarozole orally. Tumor growth is monitored, and the levels of retinoic acid in the tumors are measured. The compound's ability to inhibit tumor growth and increase retinoic acid levels is assessed. |
| ADME/Pharmacokinetics |
Liarozole has a molecular weight of 308.76 g/mol and a molecular formula of C17H13ClN4. It is an imidazole derivative and is orally active. It is soluble in DMSO. Detailed PK parameters such as half-life and bioavailability are not extensively detailed in the provided search results.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for liarozole are not provided in the search results. As a CYP26 inhibitor and aromatase inhibitor, its safety profile would be a key consideration. Potential side effects could be related to elevated retinoic acid levels, such as mucocutaneous and skeletal effects. The compound is intended for research use only and is not for human consumption.
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| References |
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| Additional Infomation |
Liarozole belongs to the benzimidazole class of drugs. Liarozole has been used in clinical trials for the treatment of lamellar ichthyosis. Liarozole is an orally effective benzimidazole derivative with potential antitumor activity. As a retinoic acid metabolism blocker, Liarozole inhibits cytochrome P450-dependent all-trans retinoic acid (ATRA)-4-hydroxylase, thereby increasing the production of endogenous ATRA, inhibiting cell proliferation, and inducing cell differentiation. The drug also inhibits aromatase, the enzyme that catalyzes the rate-limiting step in estrogen biosynthesis. See also: Liarozole hydrochloride (note moved to).
Liarozole is an imidazole derivative and orally active retinoic acid metabolism-blocking agent (RAMBA). It inhibits CYP26-dependent 4-hydroxylation of retinoic acid with an IC50 of 7 μM. It also inhibits aromatase. It is a benzimidazole derivative with the CAS number 115575-11-6 and is supplied for research purposes. |
| Molecular Formula |
C17H13N4CL.HCL
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|---|---|
| Molecular Weight |
345.22586
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| Exact Mass |
308.083
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| CAS # |
115575-11-6
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| Related CAS # |
Liarozole dihydrochloride;1883548-96-6
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| PubChem CID |
60652
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.36g/cm3
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| Boiling Point |
578.2ºC at 760mmHg
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| Flash Point |
303.5ºC
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| Vapour Pressure |
9.2E-13mmHg at 25°C
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| LogP |
4.05
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
380
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UGFHIPBXIWJXNA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13ClN4/c18-14-3-1-2-12(8-14)17(22-7-6-19-11-22)13-4-5-15-16(9-13)21-10-20-15/h1-11,17H,(H,20,21)
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| Chemical Name |
6-[(3-chlorophenyl)-imidazol-1-ylmethyl]-1H-benzimidazole
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~323.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8966 mL | 14.4831 mL | 28.9662 mL | |
| 5 mM | 0.5793 mL | 2.8966 mL | 5.7932 mL | |
| 10 mM | 0.2897 mL | 1.4483 mL | 2.8966 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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