| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Talarozole targets cytochrome P450 enzyme isoforms CYP26A1 and CYP26B1, which are responsible for the metabolism of retinoic acid. As a retinoic acid metabolism blocking agent (RAMBA), Talarozole inhibits CYP26-mediated breakdown of endogenous all-trans-retinoic acid. Talarozole inhibits CYP26A1 with an IC50 of 5.4 nM and CYP26B1 with an IC50 of 0.46 nM. By blocking retinoic acid metabolism, the compound increases intracellular levels of retinoic acid, enhancing its biological effects.
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| ln Vitro |
HepG2 cells treated with atRA and Talarozole (1 μM) together resulted in a considerable reduction in the synthesis of 4-OH-RA and 4-oxo-RA [2].
In vitro, Talarozole potently inhibits CYP26A1 and CYP26B1 with IC50 values of 5.4 nM and 0.46 nM, respectively. The compound functions as a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans-retinoic acid. By inhibiting retinoic acid metabolism, Talarozole increases intracellular levels of endogenous all-trans retinoic acid (RA). These in vitro properties establish Talarozole as a valuable tool for studying retinoic acid signaling and for therapeutic applications in skin disorders. |
| ln Vivo |
Maximum inhibition of CYP26 activity is predicted to be 84% at 0.5 hours postdose based on a Talarozole (TLZ) Cmax of 80 nM and a Ki of 1 nM after a single dosage of Talarozole. Owing to the brief half-life of talazole (2.2 hours), it is anticipated that CYP26 activity will reach 100% again in 12 hours. Anticipating this, atRA concentrations rose by 82%, 63%, and 60% in the blood, liver, and testis, respectively, four hours after dosage; after twenty-four hours, concentrations returned to baseline. Following many doses of talarozole, there was a rise in hepatic CYP26 mRNA and activity, which may indicate that elevated atRA concentrations induced CYP26. atRA concentrations were consistently higher in the liver and serum at all time periods that were tested. Comparing atRA concentrations to control animals, higher levels were linked to higher levels of the mitochondrial biogenesis markers PGC-1β and NRF-1 mRNA [3].
In vivo, Talarozole has been studied for the treatment of acne, psoriasis, and other keratinization disorders. As an oral systemic RAMBA, the compound increases retinoic acid levels in target tissues, enhancing its biological effects. Talarozole has been investigated in clinical studies for plaque psoriasis. The compound's ability to alleviate hyperproliferation and normalize differentiation of the epidermis makes it a promising candidate for dermatological applications. |
| Enzyme Assay |
Enzyme activity assays for Talarozole are performed using purified recombinant CYP26A1 and CYP26B1 enzymes. CYP26 activity is measured by monitoring the metabolism of retinoic acid to its hydroxylated metabolites. Talarozole is incubated with the enzyme and substrate at varying concentrations in appropriate assay buffer. The reaction is stopped, and metabolite formation is quantified by HPLC or LC-MS. IC50 values are calculated from concentration-response curves. Nonspecific activity is determined in control reactions without inhibitor.
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| Cell Assay |
Cellular assays for Talarozole are performed using cell lines that express CYP26 enzymes, such as keratinocytes or other skin cells. Cells are cultured in appropriate media and treated with Talarozole at varying concentrations for defined time periods. Retinoic acid metabolism is assessed by measuring the levels of retinoic acid and its metabolites in cell lysates or culture supernatant using HPLC or LC-MS. Retinoic acid signaling is assessed by measuring the expression of retinoic acid-responsive genes by qRT-PCR. Cell proliferation and differentiation may also be assessed.
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| Animal Protocol |
In vivo studies with Talarozole are conducted in animal models of psoriasis and other skin disorders. Talarozole is administered via oral routes at defined doses and schedules. Skin hyperproliferation and differentiation are assessed by histological analysis and immunohistochemistry. Epidermal thickness and keratinocyte differentiation markers are measured. Pharmacokinetic parameters are determined from plasma samples collected at various time points. The compound has been studied in clinical trials for plaque psoriasis.
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| ADME/Pharmacokinetics |
Talarozole has a molecular weight of 377.51 and a molecular formula of C21H23N5S. The compound is an oral systemic RAMBA that inhibits CYP26A1 and CYP26B1 with IC50 values of 5.4 nM and 0.46 nM, respectively. Detailed pharmacokinetic parameters, including oral bioavailability and half-life, have been characterized in preclinical and clinical studies. The compound is soluble in DMSO. It should be stored at -20degC.
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| Toxicity/Toxicokinetics |
Talarozole has been studied in clinical trials for safety and efficacy in psoriasis and other skin disorders. The compound is intended for research use only and is not approved for human therapeutic applications. Common side effects associated with retinoid-based therapies may include skin dryness and irritation. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment. The compound has a purity of ≥98%.
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| References |
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| Additional Infomation |
N-{4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl}-1,3-benzothiazol-2-amine belongs to the benzothiazolium class of compounds, namely 2-amino-1,3-benzothiazolium, in which one amino hydrogen atom is replaced by 4-[2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl]phenyl. It belongs to the triazole, benzothiazolium, aromatic amine, and secondary amine classes. Taprazole has been studied for the treatment of psoriasis and skin inflammation. Mechanism of Action: Lanpazol is a new generation all-trans retinoic acid metabolism blocker with high specificity for retinoic acid 4-hydroxylase. This drug can reduce excessive epidermal proliferation and normalize epidermal differentiation in animal models of psoriasis. All-trans retinoic acid (RA) regulates epithelial cell differentiation and growth by activating specific nuclear RA receptors (RAR). Lanbazol's mechanism of action is to inhibit the metabolic breakdown of retinoic acid, thereby enhancing the biological efficacy of RA.
Talarozole (R115866) is an oral systemic all-trans retinoic acid metabolism blocking agent (RAMBA) that inhibits CYP26A1 and CYP26B1 with IC50 values of 5.4 nM and 0.46 nM, respectively. The compound increases intracellular levels of endogenous all-trans retinoic acid (RA). Talarozole has been studied for the treatment of acne, psoriasis, and other keratinization disorders. The compound is for research purposes only. |
| Molecular Formula |
C21H23N5S
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| Molecular Weight |
377.50582
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| Exact Mass |
377.167
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| CAS # |
201410-53-9
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| Related CAS # |
(+)-Talarozole;201410-66-4;(-)-Talarozole;201410-67-5;Talarozole (R enantiomer);870093-23-5
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| PubChem CID |
9799888
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| Appearance |
White to off-white solid powder
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| LogP |
5.73
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
452
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC(CC)C(C1=CC=C(C=C1)NC2=NC3=CC=CC=C3S2)N4C=NC=N4
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| InChi Key |
SNFYYXUGUBUECJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H23N5S/c1-3-15(4-2)20(26-14-22-13-23-26)16-9-11-17(12-10-16)24-21-25-18-7-5-6-8-19(18)27-21/h5-15,20H,3-4H2,1-2H3,(H,24,25)
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| Chemical Name |
N-[4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl]-1,3-benzothiazol-2-amine
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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 : ~33.33 mg/mL (~88.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (5.30 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 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 mg/mL (5.30 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 20.0 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 | 2.6489 mL | 13.2447 mL | 26.4894 mL | |
| 5 mM | 0.5298 mL | 2.6489 mL | 5.2979 mL | |
| 10 mM | 0.2649 mL | 1.3245 mL | 2.6489 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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