Talarozole |
Catalog No.GC17063
One-Click Copy Product Info
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Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 201410-53-9
Sample solution is provided at 25 µL, 10mM.
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Talarozole is a selective inhibitor of cytochrome P450 with an IC50 at 4 nM [1].
Cytochrome P450 is concerned with oxidative metabolism of many organic chemicals of diverse structure,both in exogenous and endogenous environment. Cytochrome P450 are notable both for the diversity of reactions that they catalyze and the range of chemically dissimilar substrates upon which they act.
Talarozole is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans-retinoic acid for the treatment of psoriasis and acne. Talarozole treatment increased the mRNA expression of CRABP2, KRT4, CYP26A1 and CYP26B1 dose, meanwhile, compared with vehicle-treated skin, decreased the expression of KRT2 and IL-1α. There was no mRNA change in retinol-metabolizing enzymes. No induction of epidermal thickness or overt skin inflammation in talarozole-treated skin. Immunofluorescence analysis substantiated an upregulation of KRT4 protein, however, there were no upregulation of CYP26B1 and CYP26A1 expression was found.[1, 2]
There were 0.1% of the dose found in the skin itself after 12-24 h. The results of distribution of talarozole within the skin show that 80% was located in the epidermis, meanwhile, the remaining 20% was detected in the dermis. [3]
References:
[1] Pavez Loriè E, Cools M, Borgers M, Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis. The British Journal of Dermatology,2009,160(1):
26-36.
[2] Geria AN, Scheinfeld NS. Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne. Current Opinion In Investigational Drugs,2008 ,9(11):1228-1237.
[3] Baert B, De Spiegeleer B. Local skin pharmacokinetics of talarozole, a new retinoic acid metabolism-blocking agent. Skin Pharmacol Physiol,2011,24(3):151-159
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Cell experiment: |
Human liver microsomes (0.2 mg/mL) are incubated with 4-OH-atRA (500 nM) and NADPH, NADP+ or NAD+ (each at 2 mM) in 100 mM KPi buffer pH 7.4. In addition, 4-OH-atRA is incubated with human liver microsomes in the presence and absence of Talarozole (1 μM), a CYP26A1 specific inhibitor, and Ketoconazole (10 μM) a pan-P450 inhibitor and with NADPH as a cofactor. Following a 5 min pre-incubation, the reactions are initiated with the addition of cofactor and incubated for 30 minutes. At 30 min the reactions are quenched with equal volume of Acetonitrile and centrifuged at 3,000 g for 15 min. The supernatants are collected and 4-oxo-atRA formation is analyzed by LC-MS/MS. All incubations are normalized to a no cofactor control[2]. |
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Animal experiment: |
Mice[3]Talarozole is administered to mice as a single dose (2.5 mg/kg) or as multiple doses for three days. Serum Talarozole concentrations and serum, liver and testes atRA concentrations are measured by LC-MS/MS. Inhibition of CYP26 and changes inatRA concentrations in each tissue are predicted based on CYP26 activity in vitro and Talarozole disposition. Markers of fatty acid oxidation in the liver and spermatogonial differentiation in the testes are measured following Talarozole treatment. |
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References: [1]. Diaz P, et al. Development and Characterization of Novel and Selective Inhibitors of Cytochrome P450 CYP26A1, theHuman Liver Retinoic Acid Hydroxylase. J Med Chem. 2016 Mar 24;59(6):2579-95. |
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| Cas No. | 201410-53-9 | SDF | |
| Chemical Name | N-[4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl]-1,3-benzothiazol-2-amine | ||
| Canonical SMILES | CCC(CC)C(C1=CC=C(C=C1)NC2=NC3=CC=CC=C3S2)N4C=NC=N4 | ||
| Formula | C21H23N5S | M.Wt | 377.51 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6489 mL | 13.2447 mL | 26.4894 mL |
| 5 mM | 529.8 μL | 2.6489 mL | 5.2979 mL |
| 10 mM | 264.9 μL | 1.3245 mL | 2.6489 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >97.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)