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Identification of two HIV inhibitors that also inhibit human RNaseH2

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Molecules and Cells

Abstract

A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 μM and 16 μM, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 μM, 7.9 μM, and 31.7 μM, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.

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Authors and Affiliations

  1. Drug Biology Group, Institut Pasteur Korea, Seongnam, 463-400, Korea

    Junghwan Kim, Jaewan Yoon, MoonKyeong Ju, Yunmi Lee & Sung-Jun Han

  2. Screening Technology Platforms Group, Institut Pasteur Korea, Seongnam, 463-400, Korea

    Tae-Hee Kim & Jonathan Cechetto

  3. Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea

    Tae-Hee Kim

  4. Medicinal Chemistry Group, Institute Pasteur Korea, Seongnam, 463-400, Korea

    Junwon Kim & Zaesung No

  5. Cell Biology of Retroviruses Group, Institut Pasteur Korea, Seongnam, 463-400, Korea

    Peter Sommer

  6. Department of Biological Sciences, Konkuk University, Seoul, 143-701, Korea

    Sung-Jun Han

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  1. Junghwan Kim
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  2. Jaewan Yoon
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  3. MoonKyeong Ju
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  4. Yunmi Lee
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  5. Tae-Hee Kim
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  6. Junwon Kim
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  7. Peter Sommer
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  8. Zaesung No
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  9. Jonathan Cechetto
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  10. Sung-Jun Han
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Correspondence to Sung-Jun Han.

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Kim, J., Yoon, J., Ju, M. et al. Identification of two HIV inhibitors that also inhibit human RNaseH2. Mol Cells 36, 212–218 (2013). https://doi.org/10.1007/s10059-013-2348-z

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  • DOI: https://doi.org/10.1007/s10059-013-2348-z

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