Jingui Ma

Chinese Academy of Sciences, Peping, Beijing, China

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Publications (3)9.82 Total impact

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    ABSTRACT: We report here the discovery of novel purine derivatives with potent and selective inhibitory activity against c-Src tyrosine kinase by adopting a strategy integrating focused combinatorial library design, virtual screening, chemical synthesis, and bioassay. Thirty two compounds were selected and synthesized. All compounds showed potent inhibitory activity against c-Src kinase with IC₅₀ values ranging from 3.14 μM to 0.02 μM. Compound 5i was identified as one of the most potent agent with an IC₅₀ 120 times lower than those of the hits. The high hit rate (100%) and the potency of the new Src kinase inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening. The novel active chemical entities reported here should be good leads for further development of purine-based anticancer drugs targeting Src tyrosine kinase.
    Bioorganic & medicinal chemistry 07/2010; 18(13):4615-24. · 2.82 Impact Factor
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    ABSTRACT: Quercetin-3-O-amino acid-esters, a new type of quercetin derivatives, were successfully prepared for the first time. Different from quercetin, the novel compounds show higher selectivity as inhibitors against Src tyrosine kinase (IC50 values ranging from 3.2μM to 9.9μM) than against EGFR tyrosine kinase. Molecular docking reveals that both hydrophobic and hydrogen bonding interactions are important to the selectivity. Therefore, this study provides a new promising scaffold for further development of new anticancer drugs targeting Src tyrosine kinase.
    European journal of medicinal chemistry 01/2009; 44(5):1982-1988. · 3.27 Impact Factor
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    ABSTRACT: Despite the emerging success of multi-targeted protein tyrosine kinase (PTK) inhibitors in cancer therapy, significant side effects and resistance concerns seems to be avoided unlikely. The aim of the present study was to identify novel multi-targeting PTK inhibitors. The kinase enzymatic activities were measured by enzyme-linked immunosorbent assay (ELISA). The antiproliferative activities in human microvascular endothelial cells (HMECs) were evaluated by sulforhodamine (SRB) assay. The phosphorylation of kinases and their downstream molecules was probed by western blot analysis. The binding mode between MdOS and PTKs was profiled by surface plasmon resonance (SPR) approach and molecular simulation. Tube formation assay, rat aortic ring method and chicken chorioallantoic membrane assay were combined to illustrate the in vitro and in vivo anti-angiogenic effects. Results indicated that MdOS, a novel marine-derived oligosaccharide sulfate, exhibited a broad-spectrum PTK inhibitory action. At an enzymatic level, MdOS inhibited HER2, EGFR, VEGFR, PDGFR, c-Kit, FGFR1 and c-Src, with little impact on FGFR2. In cellular settings, MdOS inhibited phosphorylation of PTKs, exemplified by HER2, EGFR and VEGFR2, and downstream molecules of Erk1/2 and AKT. Further studies demonstrated that MdOS acted as an ATP-competitive inhibitor via directly binding to the residues of entrance rather than those of the ATP-binding pocket. Furthermore, MdOS inhibited proliferation and tube formation of HMECs, arrested microvessel outgrowth of rat aortic rings and hindered the neovascularization of chick allantoic membrane. Taken together, results presented here indicated that MdOS exhibited anti-angiogenic activity in a PTK-dependent manner and make it a promising agent for further evaluation in PTK-associated cancer therapy.
    PLoS ONE 02/2008; 3(11):e3774. · 3.73 Impact Factor

Publication Stats

27 Citations
9.82 Total Impact Points

Institutions

  • 2010
    • Chinese Academy of Sciences
      • State Key Laboratory of Drug Research
      Peping, Beijing, China
  • 2008
    • Northeast Institute of Geography and Agroecology
      • State Key Laboratory of Drug Research
      Beijing, Beijing Shi, China