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A novel small molecule inhibitor targeted at Bcl-2

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Abstract

Recently, the heterocyclic compound 8-oxo-3-thiomorpholino-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) was synthesized and shown to induce apoptosis in both (H22) hematoma and (MCF-7) adenocarcinoma cells. The IC50 values of S1 against the two cell lines were 0.17 and 0.09 μmol/L, respectively. Furthermore, the apoptosis-inducing activity of this compound was highlighted both in vivo and in vitro. Subsequent experiments identified Bcl-2 as the primary target of S1, as a significant reduction in Bcl-2 protein levels was observed in H22 cells following a two-hour treatment with 10 μmol/L S1. While rapid depolarization of mitochondrial membranes led immediately to caspase 9 activation, no changes were identified in either caspase 8 levels or levels in Bcl-2 mRNA. These data were consistent with the results of circular dichroism (CD) spectra analysis, revealing that S1 inactivated the Bcl-2 protein by destroying its critical alpha helices. Taken together, these results suggest the potential of S1 in the development of new therapeutic agents.

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Authors and Affiliations

  1. School of Environmental & Biological Science & Technology, Dalian University of Technology, Dalian, 116024, China

    Jin Liji & Wei MeiJiao

  2. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116012, China

    Zhang ZhiChao, Wang Yuanyuan & Xu Qin

  3. State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjing, China

    Zhang ZhiChao

Authors
  1. Jin Liji
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  2. Zhang ZhiChao
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  3. Wang Yuanyuan
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  4. Wei MeiJiao
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  5. Xu Qin
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Correspondence to Zhang ZhiChao.

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Supported by the National Natural Science Foundation of China (Grant No. 30400106)

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Jin, L., Zhang, Z., Wang, Y. et al. A novel small molecule inhibitor targeted at Bcl-2. SCI CHINA SER C 50, 624–629 (2007). https://doi.org/10.1007/s11427-007-0079-0

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  • DOI: https://doi.org/10.1007/s11427-007-0079-0

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