2. Academic Validation
  3. Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist

Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist

  • Bioorg Med Chem Lett. 2015 Nov 1;25(21):4838-4842. doi: 10.1016/j.bmcl.2015.06.062.
Manish K Singh 1,  Huanyao Gao 1,  Wei Sun 1,  Zhiquan Song 1,  Robert Schmalzigaug 2,  Richard T Premont 2,  Qisheng Zhang 3
Affiliations

Affiliations

  • 1 Division of Chemical Biology and Medicinal Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 2 Division of Gastroenterology, School of Medicine, Duke University, Durham, NC 27710, USA.
  • 3 Division of Chemical Biology and Medicinal Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
PMID: 26152429 DOI: 10.1016/j.bmcl.2015.06.062
Abstract

Both the Wnt/β-catenin signaling pathway and small GTPases of the ADP-ribosylation factors (ARF) family play important roles in regulating cell development, homeostasis and fate. The previous report of QS11, a small molecule Wnt synergist that binds to ARF GTPase-activating protein 1 (ARFGAP1), suggests a role for ARFGAP1 in the Wnt/β-catenin pathway. However, direct inhibition of enzymatic activity of ARFGAP1 by QS11 has not been established. Whether ARFGAP1 is the only target that contributes to QS11's Wnt synergy is also not clear. Here we present structure-activity relationship (SAR) studies of QS11 analogs in two assays: direct inhibition of enzymatic activity of purified ARFGAP1 protein and cellular activation of the Wnt/β-catenin pathway. The results confirm the direct inhibition of ARFGAP1 by QS11, and also suggest the presence of other potential cellular targets of QS11.

Keywords

ADP-ribosylation factors; GTPase-activating proteins; QS11; Structure–activity relationship (SAR); Wnt/β-catenin signaling.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-12762
    99.22%, ARFGAP1 Inhibitor