RVT-501 (E6005) is a selective phosphodiesterase 4 (PDE4) inhibitor with an IC50 of 2.8 nM.
RVT-501 potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM and suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM[1].
RVT-501 is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis. In mice models, the topical application of RVT-501 produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. On the basis of these observed effects, topical RVT-501 ameliorates the appearance of atopic dermatitis-like skin lesions in two types of AD models, hapten- and mite-elicited models, exhibiting inhibitory effects comparable to that of tacrolimus[1]. A single topical application of RVT-501 significantly inhibits spontaneous scratching during 1-2 h after application in mice with chronic dermatitis; the inhibition is partial and similar between 0.01% and 0.03%. Topical application of 0.03% RVT-501 to the rostral back significantly inhibits the increased activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP is significantly decreased in mice with chronic dermatitis, and this decrease is reversed by topical RVT-501 application[2].
References:
[1]. Ishii N, et al. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
[2]. Andoh T, et al. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61.