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AT-13148

China

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Bioactive small molecules

製品仕様

(S)-1-(4-(1H-pyrazol-4-yl)phenyl)-2-amino-1-(4-chlorophenyl)ethanol

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タイトルまたは説明

  Product NameAT13148Iupac Chemical Name(S)-1-(4-(1H-pyrazol-4-yl)phenyl)-2-amino-1-(4-chlorophenyl)ethanol SynonymsAT13148;AT-13148 Molecular FormulaC17H16ClN3O Molecular Weight313.78 SmileClC1=CC=C([C@](C2=CC=C(C3=CNN=C3)C=C2)(O)CN)C=C1InChiKeyIIRWNGPLJQXWFJ-KRWDZBQOSA-NInChiInChI=1S/C17H16ClN3O/c18-16-7-5-15(6-8-16)17(22,11-19)14-3-1-12(2-4-14)13-9-20-21-10-13/h1-10,22H,11,19H2,(H,20,21)/t17-/m0/s1Cas1056901-62-2
    Appearanceoff-white solid Purity98%;ee>98% Solubility5mg/ml in DMSO Storage3 years -20ºCpowder 6 months-80ºCin solvent Shipping ConditionShipped under ambient temperature. Quality control

     

AT13148, a first-in-class multi-AGC kinase inhibitor, against gastric cancer cells. AT13148 exerted potent cytotoxic and anti-proliferative activities against a panel human gastric cancer cell lines (HGC-27, AGS, SNU-601, N87 and MKN-28), possibly via inducing cancer cell apoptotic death. Apoptosis inhibition by the Caspase blockers dramatically attenuated AT13148-caused cytotoxicity against gastric cancer cells. Intriguingly, same AT13148 treatment was not cytotoxic/pro-apoptotic to the non-cancerous human gastric epithelial GEC-1 cells. At the signaling level, AT13148 treatment in gastric cancer cells dramatically suppressed activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3 (GSK-3) and p90 ribosomal S6 kinase (RSK). Our in vivo studies demonstrated that daily oral gavage of AT13148 at well-tolerated doses significantly inhibited HGC27 xenograft tumor growth in nude mice. AGC activity was also dramatically decreased in AT13148-administrated HGC27 tumors. Therefore, targeting AGC kinases by AT13148 demonstrates superior anti-gastric cancer activity both in vitro and in vivo. The preclinical results of this study support the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate.


 

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Wuhan Sun-shine Bio-technology Corporation Limited

連絡先担当者

Winne

会社

Wuhan Sun-shine Bio-technology Corporation Limited

住所

Wuhan, Other, China,

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