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Heat Shock Protein Inhibitors pp 197–219Cite as

HSP47: The New Heat Shock Protein Therapeutic Target

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Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 19))

Abstract

Heat shock proteins (HSPs) are part of a highly conserved genetic survival system originally discovered by Ferruccio Ritossa in 1962 (Ritossa, Riv Ist Sieroter Ital 37:79–108, 1962). Members of this family function as molecular chaperones that stabilize protein folding (De Maio, Shock 11:1–12, 1999). HSP47 is a molecular chaperone that is essential for collagen biosynthesis (Ishida et al., Mol Biol Cell 17:2346–2355, 2006; Matsuoka et al., Mol Biol Cell 15:4467–4475, 2004; Nagai et al., J Cell Biol 150:1499–1506, 2000). This chaperone is a potential therapeutic target, as it has been observed to be upregulated in collagen-producing cells in several fibrotic conditions (Taguchi et al., Acta Histochem Cytochem 44:35–41, 2011). The recent resolution of a HSP47 crystal structure has provided new insights into the chaperone’s mechanism of action (Widmer et al., Proc Natl Acad Sci U S A 109:13243–13247, 2012) with implications for future drug design. This review will summarize our current understanding of the biochemistry of HSP47-collagen interactions and the potential of HSP47 as a therapeutic target in fibrotic conditions. It will also discuss the current pharmacological inhibitors and the identification of new HSP47 small-molecule inhibitors.

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Acknowledgments

This work was supported by a Cancer Institute NSW Early Career Fellowship (G. Sharbeen) and a National Health and Medical Research Council (NHMRC) CDF Fellowship (P.A. Phillips).

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Authors and Affiliations

  1. Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia

    George Sharbeen & Phoebe Phillips

  2. School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia

    Shelli McAlpine

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  1. George Sharbeen
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Correspondence to Phoebe Phillips .

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  1. School of Chemistry, University of New South Wales, Sidney, New South Wales, Australia

    Shelli R. McAlpine

  2. Biomedical Biotechnology Research Unit (BioBRU); Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa

    Adrienne Lesley Edkins

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Sharbeen, G., McAlpine, S., Phillips, P. (2015). HSP47: The New Heat Shock Protein Therapeutic Target. In: McAlpine, S., Edkins, A. (eds) Heat Shock Protein Inhibitors. Topics in Medicinal Chemistry, vol 19. Springer, Cham. https://doi.org/10.1007/7355_2015_89

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