AS1517499

AS1517499 is a STAT6 inhibitor (IC₅₀ = 21 nM in a reporter assay).¹ It inhibits IL-4-induced Th2 differentiation (IC₅₀ = 2.3 nM), but not IL-12-induced Th1 differentiation, of mouse spleen T cells. AS1517499 (10 mg/kg) inhibits bronchial smooth muscle hyperresponsiveness and IL-13 production in ovalbumin-sensitized mice when administered one hour prior to antigen exposure.² It inhibits STAT6 phosphorylation and thyroid epithelial cell (TEC) hyperplasia and decreases serum levels of 3,3',5-triiodo-L-thyronine (T3; Item No. 16028) and thyroxine (T4) in a mouse model of Graves' disease when administered at a dose of 10 mg/kg per day.³ AS1517499 (20 mg/kg twice weekly) also inhibits tumor growth and liver metastasis in a murine orthotopic 4T1 mammary carcinoma model.⁴

WARNING This product is not for human or veterinary use.

1. Nagashima, S., Yokota, M., Nakai, E., et al. Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors. Bioorg. Med. Chem. 15(2), 1044-1055 (2006).

2. Chiba, Y., Todoroki, M., Nishida, Y., et al. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am. J. Respir. Cell Mol. Biol. 41(5), 516-524 (2009).

3. Jiang, X., Zha, B., Liu, X., et al. STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia. Cell Death Dis. 7(12), e2506 (2016).

4. Binnemars-Postma, K., Bansal, R., Storm, G., et al. Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. The FASEB Journal 32(2), 969-978 (2018).