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.