Asivatrep
(Synonyms: PAC-14028) 目录号 : GC35407
Asivatrep是一种强效、选择性、非甾体类的transient receptor potential vanilloid subfamily V member 1 (TRPV1)拮抗剂。
Cas No.:1005168-10-4
Sample solution is provided at 25 µL, 10mM.
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Asivatrep is a potent, selective, and nonsteroidal antagonist transient receptor potential vanilloid subfamily V member 1 (TRPV1) [1]. Asivatrep works by enhancing the production of key markers involved in skin differentiation, such as loricrin, filaggrin, involucrin, and certain keratins, leading to a reduction in dermatitis and pruritis[2]. Asivatrep has been widely used in various animal models to alleviate mild to moderate atopic dermatitis (AD)[3].
In vitro, Asivatrep (22.4μM) treatment for 48 hours downregulated the production of itch-related cytokines and decreased the phosphorylation level of NF-κB signaling factors in HaCaT cells[4].
In vivo, Asivatrep treatment via oral administration at a dose of 30mg/kg/day for three days significantly reduced skin itching in NC/Nga mice exposed to Dermatophagoides farina (Df) extract, alleviated mast cell degranulation, and decreased the level of IgG2a[5]. For consecutive 16 days, oral administration of 30mg/kg dose of Asivatrep daily notably inhibited the increase in trans-epidermal water loss (TEWL) in AD model mice induced by oxazolone (OXZ), and alleviated skin barrier damage[6]. For 11 consecutive days, applying 50μl of 1.0% Asivatrep cream twice daily significantly improved the skin inflammation in hairless mice induced by OXZ, reduced the thickening of the epidermis of the skin damage, and restored the barrier function of the stratum corneum[7].
References:
[1] Park C W, Kim B J, Lee Y W, et al. Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD)[J]. Journal of Allergy and Clinical Immunology, 2022, 149(4): 1340-1347. e4.
[2] Shergill M, Bajwa B, Yilmaz O, et al. Biologic and small molecule therapy in atopic dermatitis[J]. Biomedicines, 2024, 12(8): 1841.
[3] Choi J K, Cho W, Lee J H, et al. A TRPV1 antagonist, PAC-14028 does not increase the risk of tumorigenesis in chemically induced mouse skin carcinogenesis[J]. Regulatory Toxicology and Pharmacology, 2020, 112: 104613.
[4] Yoon J H, Woo B Y, Kim M Y, et al. Attenuation of senile pruritus by PAC-14028-mediated downregulation of the NF-κB and MAPK pathways[J]. International Journal of Immunopathology and Pharmacology, 2025, 39: 03946320251321354.
[5] Yun J W, Seo J A, Jang W H, et al. Antipruritic effects of TRPV1 antagonist in murine atopic dermatitis and itching models[J]. Journal of investigative dermatology, 2011, 131(7): 1576-1579.
[6] Yun J W, Seo J A, Jeong Y S, et al. TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery[J]. Journal of dermatological science, 2011, 62(1): 8-15.
[7] Lee J H, Choi C S, Bae I H, et al. A novel, topical, nonsteroidal, TRPV1 antagonist, PAC-14028 cream improves skin barrier function and exerts anti-inflammatory action through modulating epidermal differentiation markers and suppressing Th2 cytokines in atopic dermatitis[J]. Journal of Dermatological Science, 2018, 91(2): 184-194.
Asivatrep是一种强效、选择性、非甾体类的transient receptor potential vanilloid subfamily V member 1 (TRPV1)拮抗剂[1]。Asivatrep通过增强皮肤分化相关关键标志物的产生发挥作用，例如兜甲蛋白、丝聚蛋白、包膜蛋白和某些角蛋白，从而减轻皮炎和瘙痒[2]。Asivatrep已广泛用于各种动物模型中，以缓解轻度至中度特应性皮炎（AD）[3]。
在体外，Asivatrep（22.4μM）处理48小时下调了HaCaT细胞中瘙痒相关细胞因子的产生，并降低了NF-κB信号通路因子的磷酸化水平[4]。
在体内，以30mg/kg/day的剂量口服Asivatrep连续三天，显著减少了暴露于Dermatophagoides farina (Df)提取物的NC/Nga小鼠的皮肤瘙痒，缓解了肥大细胞脱颗粒，并降低了IgG2a水平[5]。连续16天每日口服30mg/kg剂量的Asivatrep显著抑制了恶唑酮（OXZ）诱导的AD模型小鼠经表皮水分流失(TEWL)的增加，并缓解了皮肤屏障损伤[6]。连续11天每日两次涂抹50μl的1.0%的Asivatrep乳膏显著改善了OXZ诱导的无毛小鼠皮肤炎症，减少了皮损处表皮的增厚，并恢复了角质层的屏障功能[7]。
| Cell experiment [1]: | |
Cell lines | HaCaT cells |
Preparation Method | HaCaT cells were seeded at a density of 4×105 cells per well in a 6-well plate. Cells were cultured in DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin in a 5% CO2 incubator overnight. Subsequently, the cells were incubated with different concentrations of Asivatrep (0, 5.6, 11.2, 22.4µM) for 2 hours, followed by incubation with 20nM IL-17A for 2 hours. The expression of TRPV1 and inflammatory factors was then analyzed. |
Reaction Conditions | 0, 5.6, 11.2, 22.4µM; 2h |
Applications | Asivatrep treatment reduced TRPV1, IL-4, and IL-13 mRNA expression in HaCaT cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female hairless mice |
Preparation Method | Female hairless mice (7 weeks old) were raised in a controlled environment (23±3°C, relative humidity 40–60%, 12/12 light-dark cycle), with ad free access to laboratory feed and tap water. On day 0, 50μl of 5% OXZ solution was applied to the neck of the hairless mice for sensitization, and then 100μl of 0.1% OXZ solution was applied to both sides of the mice every day for 15 days. From the day before the first OXZ sensitization to the day of sacrifice, mice were given Asivatrep (30mg/kg/day; p.o.) every day for 16 days. After the treatment, the TEWL on the back of the mice, the thickness of skin inflammation, and the severity of AD-like symptoms were measured. |
Dosage form | 30mg/kg/day for 16 days; p.o. |
Applications | Asivatrep inhibited the increase in TEWL in AD model mice, and alleviated the general AD-like symptoms, including serum IgE increase, mast cell degranulation, scratching behavior and clinical severity of dermatitis. |
References: | |
| Cas No. | 1005168-10-4 | SDF | |
| 别名 | PAC-14028 | ||
| Canonical SMILES | O=C(N[C@@H](C1=CC(F)=C(NS(=O)(C)=O)C(F)=C1)C)/C=C/C2=CC=C(C(F)(F)F)N=C2CCC | ||
| 分子式 | C21H22F5N3O3S | 分子量 | 491.47 |
| 溶解度 | DMSO: 50 mg/mL (101.74 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0347 mL | 10.1736 mL | 20.3471 mL |
| 5 mM | 406.9 μL | 2.0347 mL | 4.0694 mL |
| 10 mM | 203.5 μL | 1.0174 mL | 2.0347 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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