AS1517499

• CAT Number: I005481
• CAS Number: 919486-40-1
• Molecular Formula: C20H20ClN5O2
• Molecular Weight: 397.86
• Purity: ≥95%
• Target: STAT6
• Solubility: DMSO: ≥ 35 mg/mL
• Storage: Desiccate at +4C
• IC50: 21 nM (STAT6)
• InChI: InChI=1S/C20H20ClN5O2/c21-16-10-13(6-7-17(16)27)8-9-23-20-25-12-15(18(22)28)19(26-20)24-11-14-4-2-1-3-5-14/h1-7,10,12,27H,8-9,11H2,(H2,22,28)(H2,23,24,25,26)
• InChIKey: OZRMEKAUZBKTTC-UHFFFAOYSA-N
• SMILES: c1ccc(cc1)CNc2c(cnc(n2)NCCc3ccc(c(c3)Cl)O)C(=O)N

AS1517499(CAT: I005481) is a chemical compound known as a potent inhibitor of STAT6 (Signal Transducer and Activator of Transcription 6). STAT6 is a transcription factor involved in the signaling pathway of certain immune cells, particularly those involved in allergic and inflammatory responses. By inhibiting STAT6, AS1517499 may modulate the activity of these immune cells and potentially impact allergic and inflammatory conditions.

Reference

1:Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24. doi: 10.1165/rcmb.2008-0163OC. Epub 2009 Feb 6. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice.Chiba Y,Todoroki M,Nishida Y,Tanabe M,Misawa M, PMID: 19202006 DOI: 10.1165/rcmb.2008-0163OC Abstract: Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. The signal transducer and activation of transcription 6 (STAT6) is one of the major signal transducers activated by IL-13, and a possible involvement of IL-13/STAT6 pathway in the augmented bronchial smooth muscle (BSM) contraction has been suggested. In the present study, the effect of a novel STAT6 inhibitor, AS1517499, on the development of antigen-induced BSM hyperresponsiveness was investigated. In cultured human BSM cells, IL-13 (100 ng/ml) caused a phosphorylation of STAT6 and an up-regulation of RhoA, a monomeric GTPase responsible for Ca2+ sensitization of smooth muscle contraction: both events were inhibited by co-incubation with AS1517499 (100 nM). In BALB/c mice that were 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 were observed after the last antigen challenge. These mice had 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 inhibited both the antigen-induced up-regulation of RhoA and BSM hyperresponsiveness, almost completely. A partial but significant inhibition of antigen-induced production of IL-13 was also found. These findings suggest that the inhibitory effects of STAT6 inhibitory agents, such as AS1517499, both on RhoA and IL-13 up-regulations might be useful for asthma treatment.