| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Talarozole, formerly known as R115866, is a novel, potent and orally bioavailable CYP26 inhibitor under development for the treatment of acne, psoriasis and other keratinization disorders. Talarozole inhibits the metabolism of retinoic acid by blocking the cytochrome P450 enzyme isoform CYP26, a retinoic acid hydroxylase. Because of this mechanism, it is called a retinoic acid metabolism blocking agent (RAMBA).
| 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].
|
|---|---|
| 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].
|
| 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.
[2]. Topletz AR, et al. Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in theelimination of active retinoids. Mol Pharmacol. 2015;87(3):430-41. [3]. Faith Stevison, et al. CYP26 Inhibition Increases Retinoic Acid Concentrations in Target Tissues and Alters Retinoid Signaling [4]. Tripathy S, et al.All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver. Mol Pharmacol. 2016 May;89(5):560-74. [5]. Bovenschen HJ, et al. Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study. Br J Dermatol. 2007 Feb;156(2):263-70 |
| Molecular Formula |
C21H23N5S
|
|---|---|
| Molecular Weight |
377.50582
|
| CAS # |
201410-53-9
|
| Related CAS # |
(+)-Talarozole;201410-66-4;(-)-Talarozole;201410-67-5;Talarozole (R enantiomer);870093-23-5
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
CCC(CC)C(C1=CC=C(NC2=NC3=CC=CC=C3S2)C=C1)N4N=CN=C4
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~88.29 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
