AS1517499

AS1517499 is a potent and brain-permeable STAT6 phosphorylation inhibitor with an IC₅₀ of 21 nM. IC50 & Target: IC50: 21 nM (STAT6)^[1] In Vitro: AS1517499 shows potent STAT6 inhibition with an IC₅₀ value of 21 nM, and also inhibits IL-4-induced Th2 differentiation of mouse spleen T cells with an IC₅₀ value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12. AS1517499 selectively inhibits Th2 differentiation without affecting Th1 differentiation^[1]. In cultured human BSM cells, IL-13 (100 ng/mL) causes a phosphorylation of STAT6 and an up-regulation of RhoA, a monomeric GTPase responsible for Ca²⁺ sensitization of smooth muscle contraction: both events are inhibited by co-incubation with AS1517499 (100 nM)^[2]. In Vivo: In BALB/c mice that are actively sensitized and repeatedly challenged with ovalbumin antigen, an increased IL-13 level in bronchoalveolar lavage fluids and a phosphorylation of STAT6 in bronchial tissues are observed after the last antigen challenge. These mice have an augmented BSM contractility to acetylcholine together with an up-regulation of RhoA in bronchial tissues. Intraperitoneal injections of AS1517499 (10 mg/kg) 1 hour before each ovalbumin exposure inhibits both the antigen-induced up-regulation of RhoA and BSM hyperresponsiveness, almost completely^[2].