5-PyriMidinecarboxaMide, 2-[[2-(3-chloro-4-hydroxyphenyl)ethyl]aMino]-4-[(phenylMethyl)aMino]- Chemical Properties

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

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

5-PyriMidinecarboxaMide, 2-[[2-(3-chloro-4-hydroxyphenyl)ethyl]aMino]-4-[(phenylMethyl)aMino]- Usage And Synthesis

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

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