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]。