| Identification | Back Directory | [Name]
5-PyriMidinecarboxaMide, 2-[[2-(3-chloro-4-hydroxyphenyl)ethyl]aMino]-4-[(phenylMethyl)aMino]- | [CAS]
919486-40-1 | [Synonyms]
CS-2440
AS 1517499
AS-1517499;AS 1517499
AS-1517499; AS1517499; AS 1517499;919486-40-1
4-(Benzylamino)-2-((3-chloro-4-hydroxyphenethyl)amino)pyrimidine-5-carboxamide
5-PyriMidinecarboxaMide, 2-[[2-(3-chloro-4-hydroxyphenyl)ethyl]aMino]-4-[(phenylMethyl)aMino]- | [Molecular Formula]
C20H20ClN5O2 | [MDL Number]
MFCD24038757 | [MOL File]
919486-40-1.mol | [Molecular Weight]
397.86 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMF: 25mg/mL; DMF:PBS (pH 7.2) (1:6): 0.14mg/mL; DMSO: 15mg/mL; Ethanol: 5mg/mL | [form ]
powder | [color ]
white to beige | [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]
C1(NCCC2=CC=C(O)C(Cl)=C2)=NC=C(C(N)=O)C(NCC2=CC=CC=C2)=N1 |
| Hazard Information | Back Directory | [Description]
AS1517499 is a STAT6 inhibitor (IC50 = 21 nM in a reporter assay). 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. It inhibits STAT6 phosphorylation and thyroid epithelial cell (TEC) hyperplasia and decreases serum levels of 3,3'',5-triiodo-L-thyronine (T3; ) and thyroxine (T4) in a mouse model of Graves'' disease when administered at a dose of 10 mg/kg per day. AS1517499 (20 mg/kg twice weekly) also inhibits tumor growth and liver metastasis in a murine orthotopic 4T1 mammary carcinoma model. | [Uses]
AS1517499 is a potent and brain-permeable STAT6 phosphorylation inhibitor with an IC50 of 21 nM. | [Biochem/physiol Actions]
AS1517499 moderately inhibits the expression of RhoA (ras homolog family member A). Overexpression of RhoA protein is associated with allergic bronchial asthma. | [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]. | [IC 50]
STAT6: 21 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Nagashima S, et al. Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors. Bioorg Med Chem. 2007 Jan 15;15(2):1044-55. DOI:10.1016/j.bmc.2006.10.015
[2] Chiba Y, et al. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24. DOI:10.1165/rcmb.2008-0163OC |
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Sigma-Aldrich
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021-61415566 800-8193336 |
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https://www.sigmaaldrich.cn |
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