AS1517499 is a potent and brain-permeable STAT6 phosphorylation inhibitor with an IC50 of 21 nM.
体外研究
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. 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 Ca sensitization of smooth muscle contraction: both events are inhibited by co-incubation with AS1517499 (100 nM).
体内研究
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.
分子式
C20H20ClN5O2
分子量
397.86
CAS号
919486-40-1
运输条件
Room temperature in continental US; may vary elsewhere.