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Asivatrep (PAC 14028) is novel, potent and selective TRPV1 (transient receptor potential vanilloid type I) antagonist. It can be potentially used for the treatment of pruritus and acne
Physicochemical Properties
| Molecular Formula | C21H22F5N3O3S |
| Molecular Weight | 491.4747 |
| Exact Mass | 491.13 |
| CAS # | 1005168-10-4 |
| PubChem CID | 56649347 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.544 |
| LogP | 3.71 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 33 |
| Complexity | 775 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CCCC1=C(C=CC(=N1)C(F)(F)F)/C=C/C(=O)N[C@H](C)C2=CC(=C(C(=C2)F)NS(=O)(=O)C)F |
| InChi Key | UKGJZDSUJSPAJL-YPUOHESYSA-N |
| InChi Code | InChI=1S/C21H22F5N3O3S/c1-4-5-17-13(6-8-18(28-17)21(24,25)26)7-9-19(30)27-12(2)14-10-15(22)20(16(23)11-14)29-33(3,31)32/h6-12,29H,4-5H2,1-3H3,(H,27,30)/b9-7+/t12-/m1/s1 |
| Chemical Name | (R,E)-N-(1-(3,5-difluoro-4-(methylsulfonamido)phenyl)ethyl)-3-(2-propyl-6-(trifluoromethyl)pyridin-3-yl)acrylamide |
| Synonyms | PAC 14028 PAC-14028 PAC14028 Asivatrep |
| 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) |
Biological Activity
| ln Vitro | Asivatrep (PAC-14028) has the potential to cure atopic dermatitis since it avoids barrier degradation, speeds up skin barrier healing, and reduces itching. It has the ability to suppress the rise in serum IgE, mast cell degranulation, and infiltration of epidermal inflammatory cells linked to atopic dermatitis [1]. Asivatrep (PAC-14028) has demonstrated effectiveness in a number of illness models, such as inflammatory pain, visceral pain, and inflammatory bowel disease [2]. |
| ln Vivo | Asivatrep's (PAC-14028) plasma half-life in rats was 2.1 hours, whereas in minipigs, it was somewhat longer at 3.8 hours. In rats and minipigs, the oral bioavailability of a 10 mg/kg dosage was 52.7% and 64.2%, respectively. These results suggest that Asivatrep (PAC-14028) is comparatively well absorbed when taken orally [1]. At submicromolar concentrations, asivatrep (PAC-14028) prevents the calcium influx in keratinocytes that is triggered by capsaicin. In vivo, this strong TRPV1 antagonistic activity in keratinocytes is demonstrated by blocking capsaicin-induced increases in blood perfusion and speeding up the healing of the damaged barrier caused by tape stripping in hairless mice [3]. |
| References |
[1]. Oral and topical pharmacokinetic studies of a novel TRPV1 antagonist, PAC-14028 in rats and minipigs using liquid chromatography/tandem mass spectrometric method. J Pharm Biomed Anal. 2012 Mar 5;61:8-14. [2]. Development of PAC-14028, a novel transient receptor potential vanilloid type 1 (TRPV1) channel antagonist as a new drug for refractory skin diseases. Arch Pharm Res. 2012 Mar;35(3):393-6. [3]. TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. J Dermatol Sci. 2011 Apr;62(1):8-15. |
| Additional Infomation | PAC-14028 has been used in trials studying the treatment of Skin Pruritus, Papulopustular Rosacea, and Erythematotelangiectatic Rosacea. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~101.74 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.09 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 (5.09 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 25.0 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 | 2.0347 mL | 10.1736 mL | 20.3471 mL | |
| 5 mM | 0.4069 mL | 2.0347 mL | 4.0694 mL | |
| 10 mM | 0.2035 mL | 1.0174 mL | 2.0347 mL |