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Identification of novel inhibitors of mitogen-activated protein kinase phosphatase-1 with structure-based virtual screening

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Abstract

Mitogen-activated protein kinase phosphatase-1 (MKP-1) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. We report the first example for a successful application of the structure-based virtual screening to identify the novel inhibitors of MKP-1. It is shown that the efficiency of virtual screening can be enhanced significantly by the incorporation of a new solvation energy term in the scoring function. The newly found inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC50 values ranging from 20 to 50 μM. Therefore, they deserve a consideration for further development by structure–activity relationship studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the inhibitors in the active site of MKP-1 are discussed in detail.

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Acknowledgments

This work was supported by Grant No. K11061 from the Korea Institute of Oriental Medicine (KIOM). A Hanyang University Internal Grant also supported this study.

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul, 143-747, Korea

    Hwangseo Park

  2. Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Korea

    Jeong-Yi Jeon, Song Yi Kim & Seong Eon Ryu

  3. Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon, 305-333, Korea

    Dae Gwin Jeong

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  1. Hwangseo Park
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  2. Jeong-Yi Jeon
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Correspondence to Hwangseo Park.

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Park, H., Jeon, JY., Kim, S.Y. et al. Identification of novel inhibitors of mitogen-activated protein kinase phosphatase-1 with structure-based virtual screening. J Comput Aided Mol Des 25, 469–475 (2011). https://doi.org/10.1007/s10822-011-9432-2

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  • DOI: https://doi.org/10.1007/s10822-011-9432-2

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