HSP47: The New Heat Shock Protein Therapeutic Target

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


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.


Cancer Collagen Fibrosis Hsp47 Serpin 



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).


  1. 1.
    Ritossa P (1962) Problems of prophylactic vaccinations of infants. Riv Ist Sieroter Ital 37:79–108Google Scholar
  2. 2.
    Tissieres A, Mitchell HK, Tracy UM (1974) Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol 84:389–398CrossRefGoogle Scholar
  3. 3.
    De Maio A (1999) Heat shock proteins: facts, thoughts, and dreams. Shock 11:1–12CrossRefGoogle Scholar
  4. 4.
    Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684CrossRefGoogle Scholar
  5. 5.
    Pratt WB, Toft DO (2003) Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood) 228:111–133Google Scholar
  6. 6.
    Wegele H, Muller L, Buchner J (2004) Hsp70 and Hsp90–a relay team for protein folding. Rev Physiol Biochem Pharmacol 151:1–44Google Scholar
  7. 7.
    Arrigo AP (2005) Heat shock proteins as molecular chaperones. Med Sci (Paris) 21:619–625CrossRefGoogle Scholar
  8. 8.
    Spiess C, Meyer AS, Reissmann S et al (2004) Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Trends Cell Biol 14:598–604CrossRefGoogle Scholar
  9. 9.
    Young JC, Agashe VR, Siegers K et al (2004) Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol 5:781–791CrossRefGoogle Scholar
  10. 10.
    Adachi H, Katsuno M, Waza M et al (2009) Heat shock proteins in neurodegenerative diseases: pathogenic roles and therapeutic implications. Int J Hyperthermia 25:647–654CrossRefGoogle Scholar
  11. 11.
    Aghdassi A, Phillips P, Dudeja V et al (2007) Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res 67:616–625CrossRefGoogle Scholar
  12. 12.
    Khalil AA, Kabapy NF, Deraz SF et al (2011) Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta 1816:89–104Google Scholar
  13. 13.
    Lu X, Kakkar V (2010) The role of heat shock protein (HSP) in atherosclerosis: pathophysiology and clinical opportunities. Curr Med Chem 17:957–973CrossRefGoogle Scholar
  14. 14.
    Madrigal-Matute J, Martin-Ventura JL, Blanco-Colio LM et al (2011) Heat-shock proteins in cardiovascular disease. Adv Clin Chem 54:1–43CrossRefGoogle Scholar
  15. 15.
    Martins AS, Davies FE, Workman P (2012) Inhibiting the molecular evolution of cancer through HSP90. Oncotarget 3:1054–1056CrossRefGoogle Scholar
  16. 16.
    Kurkinen M, Taylor A, Garrels JI et al (1984) Cell surface-associated proteins which bind native type IV collagen or gelatin. J Biol Chem 259:5915–5922Google Scholar
  17. 17.
    Wang SY, Gudas LJ (1990) A retinoic acid-inducible mRNA from F9 teratocarcinoma cells encodes a novel protease inhibitor homologue. J Biol Chem 265:15818–15822Google Scholar
  18. 18.
    Cates GA, Brickenden AM, Sanwal BD (1984) Possible involvement of a cell surface glycoprotein in the differentiation of skeletal myoblasts. J Biol Chem 259:2646–2650Google Scholar
  19. 19.
    Cates GA, Kaur H, Sanwal BD (1984) Inhibition of fusion of skeletal myoblasts by tunicamycin and its reversal by N-acetylglucosamine. Can J Biochem Cell Biol 62:28–35CrossRefGoogle Scholar
  20. 20.
    Nagata K, Saga S, Yamada KM (1986) A major collagen-binding protein of chick embryo fibroblasts is a novel heat shock protein. J Cell Biol 103:223–229CrossRefGoogle Scholar
  21. 21.
    Saga S, Nagata K, Chen WT et al (1987) pH-dependent function, purification, and intracellular location of a major collagen-binding glycoprotein. J Cell Biol 105:517–527CrossRefGoogle Scholar
  22. 22.
    Ragg H (2007) The role of serpins in the surveillance of the secretory pathway. Cell Mol Life Sci 64:2763–2770CrossRefGoogle Scholar
  23. 23.
    Satoh M, Hirayoshi K, Yokota S et al (1996) Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol 133:469–483CrossRefGoogle Scholar
  24. 24.
    Ishida Y, Nagata K (2011) Hsp47 as a collagen-specific molecular chaperone. Methods Enzymol 499:167–182CrossRefGoogle Scholar
  25. 25.
    Bianchi FT, Camera P, Ala U et al (2011) The collagen chaperone HSP47 is a new interactor of APP that affects the levels of extracellular beta-amyloid peptides. PLoS One 6, e22370CrossRefGoogle Scholar
  26. 26.
    Nagai N, Hosokawa M, Itohara S et al (2000) Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis. J Cell Biol 150:1499–1506CrossRefGoogle Scholar
  27. 27.
    Matsuoka Y, Kubota H, Adachi E et al (2004) Insufficient folding of type IV collagen and formation of abnormal basement membrane-like structure in embryoid bodies derived from Hsp47-null embryonic stem cells. Mol Biol Cell 15:4467–4475CrossRefGoogle Scholar
  28. 28.
    Ishida Y, Kubota H, Yamamoto A et al (2006) Type I collagen in Hsp47-null cells is aggregated in endoplasmic reticulum and deficient in N-propeptide processing and fibrillogenesis. Mol Biol Cell 17:2346–2355CrossRefGoogle Scholar
  29. 29.
    Dafforn TR, Della M, Miller AD (2001) The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis. J Biol Chem 276:49310–49319CrossRefGoogle Scholar
  30. 30.
    Ono T, Miyazaki T, Ishida Y et al (2012) Direct in vitro and in vivo evidence for interaction between Hsp47 protein and collagen triple helix. J Biol Chem 287:6810–6818CrossRefGoogle Scholar
  31. 31.
    Gordon MK, Hahn RA (2010) Collagens. Cell Tissue Res 339:247–257CrossRefGoogle Scholar
  32. 32.
    Phillips P (2012) Pancreatic stellate cells and fibrosis. In: Grippo PJ, Munshi HG (eds) Pancreatic cancer and tumor microenvironment. Trivandrum, Transworld Research NetworkGoogle Scholar
  33. 33.
    Wynn TA, Ramalingam TR (2012) Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18:1028–1040CrossRefGoogle Scholar
  34. 34.
    Taguchi T, Nazneen A, Al-Shihri AA et al (2011) Heat shock protein 47: a novel biomarker of phenotypically altered collagen-producing cells. Acta Histochem Cytochem 44:35–41CrossRefGoogle Scholar
  35. 35.
    Schreuder HA, de Boer B, Dijkema R et al (1994) The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nat Struct Biol 1:48–54CrossRefGoogle Scholar
  36. 36.
    Irving JA, Pike RN, Lesk AM et al (2000) Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Res 10:1845–1864CrossRefGoogle Scholar
  37. 37.
    Shoulders MD, Raines RT (2009) Collagen structure and stability. Annu Rev Biochem 78:929–958CrossRefGoogle Scholar
  38. 38.
    Widmer C, Gebauer JM, Brunstein E et al (2012) Molecular basis for the action of the collagen-specific chaperone Hsp47/SERPINH1 and its structure-specific client recognition. Proc Natl Acad Sci U S A 109:13243–13247CrossRefGoogle Scholar
  39. 39.
    Drogemuller C, Becker D, Brunner A et al (2009) A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta. PLoS Genet 5, e1000579CrossRefGoogle Scholar
  40. 40.
    Yagi-Utsumi M, Yoshikawa S, Yamaguchi Y et al (2012) NMR and mutational identification of the collagen-binding site of the chaperone Hsp47. PLoS One 7, e45930CrossRefGoogle Scholar
  41. 41.
    Nishikawa Y, Takahara Y, Asada S et al (2010) A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47. Bioorg Med Chem 18:3767–3775CrossRefGoogle Scholar
  42. 42.
    Smith T, Ferreira LR, Hebert C et al (1995) Hsp47 and cyclophilin B traverse the endoplasmic reticulum with procollagen into pre-Golgi intermediate vesicles. A role for Hsp47 and cyclophilin B in the export of procollagen from the endoplasmic reticulum. J Biol Chem 270:18323–18328CrossRefGoogle Scholar
  43. 43.
    El-Thaher SH, Drake AF, Yokota S et al (1996) The pH-dependent, ATP-independent interaction of collagen specific serpin/stress protein HSP47. Protein Peptide Letters 3:1–8Google Scholar
  44. 44.
    Abdul-Wahab MF, Homma T, Wright M et al (2013) The pH sensitivity of murine heat shock protein 47 (HSP47) binding to collagen is affected by mutations in the breach histidine cluster. J Biol Chem 288:4452–4461CrossRefGoogle Scholar
  45. 45.
    Tasab M, Jenkinson L, Bulleid NJ (2002) Sequence-specific recognition of collagen triple helices by the collagen-specific molecular chaperone HSP47. J Biol Chem 277:35007–35012CrossRefGoogle Scholar
  46. 46.
    Koide T, Takahara Y, Asada S et al (2002) Xaa-Arg-Gly triplets in the collagen triple helix are dominant binding sites for the molecular chaperone HSP47. J Biol Chem 277:6178–6182CrossRefGoogle Scholar
  47. 47.
    Koide T, Asada S, Takahara Y et al (2006) Specific recognition of the collagen triple helix by chaperone HSP47: minimal structural requirement and spatial molecular orientation. J Biol Chem 281:3432–3438CrossRefGoogle Scholar
  48. 48.
    Tasab M, Batten MR, Bulleid NJ (2000) Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO J 19:2204–2211CrossRefGoogle Scholar
  49. 49.
    Crouch E (1990) Pathobiology of pulmonary fibrosis. Am J Physiol 259:L159–L184Google Scholar
  50. 50.
    Yin C, Evason KJ, Asahina K et al (2013) Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest 123:1902–1910CrossRefGoogle Scholar
  51. 51.
    Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401CrossRefGoogle Scholar
  52. 52.
    Nagata K (2003) Therapeutic strategy for fibrotic diseases by regulating the expression of collagen-specific molecular chaperone HSP47. Nihon Yakurigaku Zasshi 121:4–14CrossRefGoogle Scholar
  53. 53.
    Brown KE, Broadhurst KA, Mathahs MM et al (2005) Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver. Lab Invest 85:789–797CrossRefGoogle Scholar
  54. 54.
    Hagiwara S, Iwasaka H, Matsumoto S et al (2007) Introduction of antisense oligonucleotides to heat shock protein 47 prevents pulmonary fibrosis in lipopolysaccharide-induced pneumopathy of the rat. Eur J Pharmacol 564:174–180CrossRefGoogle Scholar
  55. 55.
    Masuda H, Fukumoto M, Hirayoshi K et al (1994) Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis. J Clin Invest 94:2481–2488CrossRefGoogle Scholar
  56. 56.
    Murakami S, Toda Y, Seki T et al (2001) Heat shock protein (HSP) 47 and collagen are upregulated during neointimal formation in the balloon-injured rat carotid artery. Atherosclerosis 157:361–368CrossRefGoogle Scholar
  57. 57.
    Naitoh M, Hosokawa N, Kubota H et al (2001) Upregulation of HSP47 and collagen type III in the dermal fibrotic disease, keloid. Biochem Biophys Res Commun 280:1316–1322CrossRefGoogle Scholar
  58. 58.
    Razzaque MS, Kumatori A, Harada T et al (1998) Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy. Nephron 80:434–443CrossRefGoogle Scholar
  59. 59.
    Razzaque MS, Nazneen A, Taguchi T (1998) Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases. Mod Pathol 11:1183–1188Google Scholar
  60. 60.
    Rocnik E, Chow LH, Pickering JG (2000) Heat shock protein 47 is expressed in fibrous regions of human atheroma and Is regulated by growth factors and oxidized low-density lipoprotein. Circulation 101:1229–1233CrossRefGoogle Scholar
  61. 61.
    Ishiwatari H, Sato Y, Murase K et al (2012) Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes. Gut. doi: 10.1136/gutjnl-2011-301746 Google Scholar
  62. 62.
    Sato Y, Murase K, Kato J et al (2008) Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol 26:431–442CrossRefGoogle Scholar
  63. 63.
    Rocnik EF, van der Veer E, Cao H et al (2002) Functional linkage between the endoplasmic reticulum protein Hsp47 and procollagen expression in human vascular smooth muscle cells. J Biol Chem 277:38571–38578CrossRefGoogle Scholar
  64. 64.
    Ishak KG, Zimmerman HJ, Ray MB (1991) Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. Alcohol Clin Exp Res 15:45–66CrossRefGoogle Scholar
  65. 65.
    Issa R, Zhou X, Constandinou CM et al (2004) Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 126:1795–1808CrossRefGoogle Scholar
  66. 66.
    Arthur MJ (2002) Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology 122:1525–1528CrossRefGoogle Scholar
  67. 67.
    Parsons CJ, Bradford BU, Pan CQ et al (2004) Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats. Hepatology 40:1106–1115CrossRefGoogle Scholar
  68. 68.
    Blomhoff R, Wake K (1991) Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 5:271–277Google Scholar
  69. 69.
    Park SJ, Sohn HY, Park SI (2013) TRAIL regulates collagen production through HSF1-dependent Hsp47 expression in activated hepatic stellate cells. Cell Signal 25:1635–1643CrossRefGoogle Scholar
  70. 70.
    Johnstone RW, Frew AJ, Smyth MJ (2008) The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 8:782–798CrossRefGoogle Scholar
  71. 71.
    Wiley SR, Schooley K, Smolak PJ et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682CrossRefGoogle Scholar
  72. 72.
    Christians ES, Yan LJ, Benjamin IJ (2002) Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. Crit Care Med 30:S43–S50CrossRefGoogle Scholar
  73. 73.
    Iwashita T, Kadota J, Naito S et al (2000) Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis. Hum Pathol 31:1498–1505CrossRefGoogle Scholar
  74. 74.
    Kakugawa T, Mukae H, Hayashi T et al (2005) Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia. Respir Res 6:57CrossRefGoogle Scholar
  75. 75.
    Amenomori M, Mukae H, Sakamoto N et al (2010) HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific interstitial pneumonia. Respir Med 104:895–901CrossRefGoogle Scholar
  76. 76.
    Kakugawa T, Yokota SI, Ishimatsu Y et al (2013) Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis. Cell Stress Chaperones. doi: 10.1007/s12192-013-0411-5 Google Scholar
  77. 77.
    Moeller A, Ask K, Warburton D et al (2008) The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int J Biochem Cell Biol 40:362–382CrossRefGoogle Scholar
  78. 78.
    Ishii H, Mukae H, Kakugawa T et al (2003) Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy. Am J Physiol Lung Cell Mol Physiol 285:L957–L963CrossRefGoogle Scholar
  79. 79.
    Kakugawa T, Mukae H, Hishikawa Y et al (2010) Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis. Virchows Arch 456:309–315CrossRefGoogle Scholar
  80. 80.
    Kakugawa T, Mukae H, Hayashi T et al (2004) Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis. Eur Respir J 24:57–65CrossRefGoogle Scholar
  81. 81.
    Vonlaufen A, Joshi S, Qu C et al (2008) Pancreatic stellate cells: partners in crime with pancreatic cancer cells. Cancer Res 68:2085–2093CrossRefGoogle Scholar
  82. 82.
    Vonlaufen A, Phillips PA, Xu Z et al (2008) Pancreatic stellate cells and pancreatic cancer cells: an unholy alliance. Cancer Res 68:7707–7710CrossRefGoogle Scholar
  83. 83.
    Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180–192CrossRefGoogle Scholar
  84. 84.
    Wang Z, Li Y, Ahmad A et al (2011) Pancreatic cancer: understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol 8:27–33CrossRefGoogle Scholar
  85. 85.
    Zalatnai A, Molnar J (2007) Review. Molecular background of chemoresistance in pancreatic cancer. In Vivo 21:339–347Google Scholar
  86. 86.
    Jacobetz MA, Chan DS, Neesse A et al (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 62:112–120CrossRefGoogle Scholar
  87. 87.
    Olive KP, Jacobetz MA, Davidson CJ et al (2009) Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324:1457–1461CrossRefGoogle Scholar
  88. 88.
    Provenzano PP, Cuevas C, Chang AE et al (2012) Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21:418–429CrossRefGoogle Scholar
  89. 89.
    Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL et al (2002) Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am J Pathol 160:1239–1249CrossRefGoogle Scholar
  90. 90.
    Maitra A, Iacobuzio-Donahue C, Rahman A et al (2002) Immunohistochemical validation of a novel epithelial and a novel stromal marker of pancreatic ductal adenocarcinoma identified by global expression microarrays: sea urchin fascin homolog and heat shock protein 47. Am J Clin Pathol 118:52–59CrossRefGoogle Scholar
  91. 91.
    McCarroll JA, Phillips PA, Santucci N et al (2006) Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis. Gut 55:79–89CrossRefGoogle Scholar
  92. 92.
    Taguchi T, Razzaque MS (2007) The collagen-specific molecular chaperone HSP47: is there a role in fibrosis? Trends Mol Med 13:45–53CrossRefGoogle Scholar
  93. 93.
    Thomson CA, Atkinson HM, Ananthanarayanan VS (2005) Identification of small molecule chemical inhibitors of the collagen-specific chaperone Hsp47. J Med Chem 48:1680–1684CrossRefGoogle Scholar
  94. 94.
    Lasky JA, Ortiz LA (2001) Antifibrotic therapy for the treatment of pulmonary fibrosis. Am J Med Sci 322:213–221CrossRefGoogle Scholar
  95. 95.
    Nagata K (1998) Expression and function of heat shock protein 47: a collagen-specific molecular chaperone in the endoplasmic reticulum. Matrix Biol 16:379–386CrossRefGoogle Scholar
  96. 96.
    Thomson CA, Ananthanarayanan VS (2001) A method for expression and purification of soluble, active Hsp47, a collagen-specific molecular chaperone. Protein Expr Purif 23:8–13CrossRefGoogle Scholar
  97. 97.
    Okano-Kosugi H, Matsushita O, Asada S et al (2009) Development of a high-throughput screening system for the compounds that inhibit collagen-protein interactions. Anal Biochem 394:125–131CrossRefGoogle Scholar
  98. 98.
    Nakayama S, Mukae H, Sakamoto N et al (2008) Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts. Life Sci 82:210–217CrossRefGoogle Scholar
  99. 99.
    Hisatomi K, Mukae H, Sakamoto N et al (2012) Pirfenidone inhibits TGF-beta1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells. BMC Pulm Med 12:24CrossRefGoogle Scholar
  100. 100.
    Cottin V (2013) The role of pirfenidone in the treatment of idiopathic pulmonary fibrosis. Respir Res 14(Suppl 1):S5Google Scholar
  101. 101.
    Chamorro A (2009) TP receptor antagonism: a new concept in atherothrombosis and stroke prevention. Cerebrovasc Dis 27(Suppl 3):20–27CrossRefGoogle Scholar
  102. 102.
    Gelosa P, Sevin G, Pignieri A et al (2011) Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis. Am J Physiol Heart Circ Physiol 300:H762–H768CrossRefGoogle Scholar
  103. 103.
    Dementiev A, Simonovic M, Volz K, Gettins PG (2003) Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases. J Biol Chem 278:37881–37887CrossRefGoogle Scholar
  104. 104.
    Bella J, Eaton M, Brodsky B, Berman HM (1994) Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. Science 266:75–81CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia
  2. 2.School of ChemistryUniversity of New South WalesSydneyAustralia

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