Protein chaperones: A composition of matter review (2008-2013)

Expert Opinion on Therapeutic Patents

Volumn 24, Issue 5, 2014, Pages 501-518

  Taldone, Tony ^a   Patel, Hardik J ^a   Bolaender, Alexander ^a   Patel, Maulik R ^a   Chiosis, Gabriela ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

ATPase; Cancer; Chaperone; Heat shock protein 70; Heat shock protein 90; Targeted therapy

Indexed keywords

ANSAMYCIN DERIVATIVE; ANTINEOPLASTIC AGENT; APTAMER; CHAPERONE; GELDANAMYCIN; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 70 INHIBITOR; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; IMIDAZOLE DERIVATIVE; IMIDAZOPYRIDINE DERIVATIVE; POLYPEPTIDE; PTERIDINE DERIVATIVE; PURINE DERIVATIVE; PYRAZOLOPYRIMIDINE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRRHOCORICIN DERIVATIVE; QUINAZOLINE DERIVATIVE; RESORCINOL DERIVATIVE; SULFONAMIDE; UNCLASSIFIED DRUG; VEMURAFENIB; HEAT SHOCK PROTEIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CELL CULTURE; CANCER INHIBITION; CD8+ T LYMPHOCYTE; COLON CANCER; DRUG BIOAVAILABILITY; DRUG DEVELOPMENT; DRUG POTENCY; DRUG SAFETY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; IC 50; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; LIVER TOXICITY; NONHUMAN; NUCLEOTIDE BINDING SITE; PHARMACOPHORE; PROTEIN ANALYSIS; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN REFOLDING; REVIEW; STRUCTURE ACTIVITY RELATION; TREATMENT RESPONSE; ANIMAL; ANTAGONISTS AND INHIBITORS; NEOPLASMS; PATENT;

ANIMALS; DRUG DISCOVERY; HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR CHAPERONES; NEOPLASMS; PATENTS AS TOPIC;

EID: 84898939969     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2014.887681     Document Type: Review

References (135)

1. Kim YE, Hipp MS, Bracher A, et al. Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem 2013;82:323-55
2. Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Cancer 2013;13:630-42
3. Santarosa M, Favaro D, Quaia M, et al. Expression of heat shock protein 72 in renal cell carcinoma: possible role and prognostic implications in cancer patients. Eur J Cancer 1997;33:873-7
4. Nanbu K, Konishi I, Mandai M, et al. Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Cancer Detect Prev 1998;22:549-55
5. Trieb K, Lechleitner T, Lang S, et al. Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. Hum Pathol 1998;29:1050-5
6. Uozaki H, Ishida T, Kakiuchi C, et al. Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Pathol Res Pract 2000;196:665-73
7. Moulick K, Ahn JH, Zong H, et al. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nat Chem Biol 2011;7:818-26
8. Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003;425:407-10
9. Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell 2008;14:250-62
10. Powers MV, Clarke PA, Workman P. Death by chaperone: HSP90, HSP70 or both? Cell Cycle 2009;8:518-26
11. Luo W, Sun W, Taldone T, et al. Heat shock protein 90 in neurodegenerative diseases. Mol Neurodegener 2010;5:24
12. Luo W, Dou F, Rodina A, et al. Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. Proc Natl Acad Sci USA 2007;104:9511-16
13. Tsan MF, Gao B. Heat shock protein and innate immunity. Cell Mol Immunol 2004;1:274-9
14. Yun TJ, Harning EK, Giza K, et al. EC144, a synthetic inhibitor of heat shock protein 90, blocks innate and adaptive immune responses in models of inflammation and autoimmunity. J Immunol 2011;186:563-75
15. Rochani AK, Singh M, Tatu U. Heat shock protein 90 inhibitors as broad spectrum anti-infectives. Curr Pharm Des 2013;19:377-86
16. Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 1998;79:129-68
17. Mayer MP. Gymnastics of molecular chaperones. Mol Cell 2010;39:321-31
18. Trepel J, Mollapour M, Giaccone G, et al. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 2010;10:537-49
19. Taipale M, Jarosz DF, Lindquist S. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol 2010;11:515-28
20. Evans CG, Chang L, Gestwicki JE. Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem 2010;53:4585-602
21. Brodsky JL, Chiosis G. Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators. Curr Top Med Chem 2006;6:1215-25
22. Garcia-Carbonero R, Carnero A, Paz-Ares L. Inhibition of HSP90 molecular chaperones: moving into the clinic. Lancet Oncol 2013;14:e358-e69
23. Jhaveri K, Taldone T, Modi S, et al. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta 2012;1823:742-55
24. Drysdale MJ, Brough PA. Medicinal chemistry of Hsp90 inhibitors. Curr Top Med Chem 2008;8:859-68
25. Janin YL. ATPase inhibitors of heatshock protein 90, second season. Drug Discov Today 2010;15:342-53
26. Janin YL. Heat shock protein 90 inhibitors. A text book example of medicinal chemistry? J Med Chem 2005;48:7503-12
27. Taldone T, Sun W, Chiosis G. Discovery and development of heat shock protein 90 inhibitors. Bioorg Med Chem 2009;17:2225-35
28. Chène P. ATPases as drug targets: learning from their structure. Nat Rev Drug Discov 2002 1 665-73
29. Brandt GEL, Blagg BSJ. Alternate strategies of Hsp90 modulation for the treatment of cancer and other diseases. Curr Top Med Chem 2009;9:1447-61
30. Patel HJ, Modi S, Chiosis G, et al. Advances in the discovery and development of heat-shock protein 90 inhibitors for cancer treatment. Expert Opin Drug Discov 2011;6:559-87
31. Messaoudi S, Peyrat JF, Brion JD, et al. Heat-shock protein 90 inhibitors as antitumor agents: a survey of the literature from 2005 to 2010. Expert Opin Ther Pat 2011;21:1501-42
32. Dymock BW, Drysdale MJ, McDonald E, et al. Inhibitors of HSP90 and other chaperones for the treatment of cancer. Expert Opin Ther Pat 2004;14:837-47
33. Biamonte MA, Van de Water R, Arndt JW, et al. Heat shock protein 90: inhibitors in clinical trials. J Med Chem 2010;53:3-17
34. Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 2012;18:64-76
35. Guo W, Reigan P, Siegel D, et al. Enzymatic reduction and glutathione conjugation of benzoquinone ansamycin heat shock protein 90 inhibitors: relevance for toxicity and mechanism of action. Drug Metab Dispos 2008;36:2050-7
36. Hansske FG, Werner S, Eckard P, et al. Synthesis of ansamycin derivatives. WO2008034895; 2008
37. Ross D, Siegel D, Guo W, et al. 19-Substituted geldanamycin derivative Hsp90 inhibitors with modified toxicity, and use in the treatment of cancers and other proliferative disorders. WO2009026548A1; 2009
38. Ross D, Siegel D, Moody CJ, et al. HSP90 inhibitors with modified toxicity. WO2013074695; 2013
39. Chiosis G, Timaul MN, Lucas B, et al. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem Biol 2001;8:289-99
40. Chiosis G, Rosen N. Small molecule compositions for binding to HSP90. WO2002036075; 2002
41. He H, Zatorska D, Kim J, et al. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J Med Chem 2006;49:381-90
42. Rodina A, Vilenchik M, Moulick K, et al. Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol 2007;3:498-507
43. Caldas-Lopes E, Cerchietti L, Ahn JH, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triplenegative breast cancer models. Proc Natl Acad Sci USA 2009;106:8368-73
44. Cerchietti LC, Lopes EC, Yang SN, et al. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat Med 2009;15:1369-76
45. Marubayashi S, Koppikar P, Taldone T, et al. HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. J Clin Invest 2010;120:3578-93
46. Kasibhatla SR, Hong K, Biamonte MA, et al. Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity. J Med Chem 2007;50:2767-78
47. Lundgren K, Zhang H, Brekken J, et al. BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol Cancer Ther 2009;8:921-9
48. Yin X, Zhang H, Lundgren K, et al. BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy. Int J Cancer 2010;126:1216-25
49. Zhang H, Neely L, Lundgren K, et al. BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance. Int J Cancer 2010;126:1226-34
50. Kim S-H, Bajji A, Tangallapally R, et al. Discovery of (2S)-1-[4-(2-{6-Amino-8- [(6-bromo-1,3- benzodioxol-5-yl) sulfanyl]-9H-purin-9- yl}ethyl)piperidin-1- yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor. J Med Chem 2012;55:7480-501
51. Immormino RM, Kang Y, Chiosis G, et al. Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90 inhibitors. J Med Chem 2006;49:4953-60
52. Chiosis G, Greengard P, Dou F, et al. Treatment of neurodegenerative diseases through inhibition of hsp90. WO2008005937; 2008
53. Chiosis G, Taldone T, Sun W. Purine derivatives useful as Hsp90 inhibitors. WO2011044394; 2011
54. Chen J, Sperl G, Gullo V, et al. Preparation of sulfamoyl-containing heterocycles as anticancer agents. WO2008049105; 2008
55. Takahashi E, Beppu T. A new nucleosidic antibiotic AT-265. J Antibiot 1982;35:939-47
56. Beautement K, Chrystal EJT, Howard J, et al. N-(alpha-aminoacyl)-5- Osulfamoyladenosines: natural product based inhibitors of amino acyl tRNA synthetases. Spec Publ R Soc Chem 2000;257:288-94
57. Qian C, Cai X, Gould S, et al. Preparation of benzodioxolyl purine derivatives as HSP90 inhibitors containing a zinc binding moiety. WO2008115262; 2008
58. Moffat DCF, Baker KWJ, Donald ADG, et al. Preparation of purine amino acid derivatives for the treatment of cancer, autoimmune and inflammatory diseases. WO2009136144; 2009
59. Bajji AC, Kim S-H, Tangallapally R, et al. Preparation of arylthiopurinamine derivatives for use as antitumor agents. WO2009065035; 2009
60. Bajji AC, Kim S-H, Markovitz B, et al. Preparation of substituted purinamines as antitumor agents. WO2007134298; 2007
61. Llauger L, He H, Kim J, et al. Evaluation of 8-arylsulfanyl, 8- arylsulfoxyl, and 8-arylsulfonyl adenine derivatives as inhibitors of the heat shock protein 90. J Med Chem 2005;48:2892-905
62. Cai X, Qian C, Zhai H. Preparation of imidazo[4,5-c]pyridine derivatives as HSP90 inhibitors. WO2008115719; 2008
63. Taldone T, Patel PD, Patel M, et al. Experimental and structural testing module to analyze paralogue- specificity and affinity in the Hsp90 inhibitors series. J Med Chem 2013;6803-18
64. Bao R, Lai C-J, Qu H, et al. CUDC- 305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res 2009;15:4046-57
65. Cai X, Qian C. Fused amino pyridines for the treatment of brain tumors. WO2010083403; 2010
66. Martinell PM, Navarro MI, Soler LM, et al. Preparation of 1H-imidazole-4- carboxamide derivatives as Hsp90 inhibitors. WO2009007399; 2009
67. Brough P, Drysdale M. Preparation of aryl-1H-pyrrolo[2,3-b]pyridine derivatives for use as HSP90 inhibitors. WO2008025947; 2008
68. Brough P, Drysdale M, Davis N. Preparation of pyrrolopyrimidine derivatives having HSP90 inhibitory activity. WO2009030871; 2009
69. Brough PA, Barril-Alonso X, Drysdale MJ. Preparation of pyrimidothiophene derivatives for use as HSP90 inhibitors. WO2006090094; 2006
70. Brough PA, Barril X, Borgognoni J, et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno [2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem 2009;52:4794-809
71. Massey AJ, Schoepfer J, Brough PA, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther 2010;9:906-19
72. Day FA, Launay DFM, Charlton MH, et al. Pyrrolo[2,3-d]pyrimidine derivatives as HSP90 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2010043867; 2010
73. Kasibhatla SR, Biamonte MA, Shi J, et al. Alkynylpyrrolo[2,3-d] pyrimidines as HSP90 inhibitors, their preparation, pharmaceutical compositions, and use in therapy. WO2006105372; 2006
74. Shi J, Van de Water R, Hong K, et al. EC144 is a potent inhibitor of the heat shock protein 90. J Med Chem 2012;55:7786-95
75. Kung P-P, Meng JJ. Preparation of 2- aminopyrimidine derivatives as HSP-90 inhibitors patent. WO2008059368; 2008
76. Kung P-P, Meng JJ. Preparation of pyrazolylethoxyphenyl pyrroloyrimidinamines as heat shock protein- 90 (HSP-90) inhibitors. WO2010018481; 2010
77. Ohsuki S, Tengeiji A, Ikeda M, et al. Preparation of pyrazolopyrimidine derivatives as inhibitors of heat shock protein 90 (HSP 90). WO2008035629; 2008
78. Ousu S, Tengeiji A, Ikeda M, et al. Preparation of pyrazolopyrimidine derivatives as inhibitors of heat shock protein 90 (HSP 90). JP2009256323; 2009
79. Ohki H, Okayama T, Ikeda M, et al. Preparation of tricyclic pyrazolopyrimidine derivatives as Hsp90 inhibitors. WO2010098344; 2010
80. Oki H, Okayama T, Ikeda M, et al. Preparation of tricyclic pyrazolopyrimidine derivatives as Hsp90 inhibitors. JP2012067087; 2012
81. Sun CL, Li X, Zhu Y. Preparation of aminopteridinone derivatives and analogs for use as HSP90 inhibitors. WO2009139834; 2009
82. Courtney SM, Whittaker M, Mather OC, et al. Preparation of 2- amino-7,8-dihydro-6H-quinazolin-5-one oximes having HSP90 inhibitory activity. WO2008142720; 2008
83. Amici R, Colombo A, Courtney SM, et al. Quinazoline derivatives with Hsp90 inhibitory activity. WO2013064919; 2013
84. Chen YK, Co EW, Guntupalli P, et al. Oxime derivatives as HSP90 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2009097578; 2009
85. Eggenweiler H-M, Sirrenberg C, Buchstaller H-P. Preparation of quinazoline amides as HSP90 modulators. WO2009010139; 2009
86. Eggenweiler H-M, Sirrenberg C, Buchstaller H-P. Preparation of quinazoline amides as HSP90 inhibitors. WO2010066324; 2010
87. Eggenweiler H-M, Sirrenberg C, Buchstaller H-P. Quinazoline derivatives as HSP90 inhibitors and their preparation and use in the treatment of diseases. WO2011060873A1; 2011
88. Eggenweiler H-M, Sirrenberg C, Buchstaller H-P. Phenylquinazoline derivatives as HSP90 inhibitors and their preparation. WO2012041435; 2012
89. Nowak T. 5,6,7,8-Tetrahydropteridine derivatives as Hsp90 inhibitors. WO2008093075; 2008
90. Schulte TW, Akinaga S, Soga S, et al. Antibiotic radicicol binds to the Nterminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 1998;3:100-8
91. Kwon HJ, Yoshida M, Fukui Y, et al. Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. Cancer Res 1992;52:6926-30
92. Ying W. Preparation of triazoles and related compounds as Hsp90 inhibitors. WO2008051416; 2008
93. Proia D, Acquaviva J. Combination therapy of Hsp90 inhibitors with BRAF inhibitors. WO2013074594; 2013
94. Ying W, Chimmanamada DU, Burlison JA, et al. Preparation of triazole compounds that modulate Hsp90 activity. WO2010017479; 2010
95. Ying W, Chimmanamada DU, Burlison JA, et al. Preparation of substituted triazoles, particularly 4,5- diphenyl-4H-1,2,4-triazole-3- carboxamides, that modulate Hsp90 activity. WO2010017545; 2010
96. Chimmanamada D, Demko Z, Ying W. Triazole derivatives as hsp90 inhibitors. WO2013148857; 2013
97. Burlison JA, Chimmanamada DU, Ying W, et al. Preparation of phenyl hydrazonamide derivatives as modulators of Hsp90 activity. WO2009158026; 2009
98. Chimmanamada DU, Ying W. Pyrrole compounds that modulate HSP90 activity. WO2009148599; 2009
99. Yang R-Y, Ali SM, Ashwell MA, et al. Preparation of substituted tetrazole compounds as HSP90 inhibitors for treating cell proliferative disorder. WO2009049305; 2009
100. Giannini G, Cabri W, Simoni D, et al. Preparation of 5-phenylisoxazole-3- carboxamides as Hsp90 modulators with antitumor activity. WO2010000748; 2010
101. Giannini G, Cabri W, Vesci L, et al. Preparation of aryl triazoles as Hsp90 inhibitors for treating cancer. WO2012084602; 2012
102. Eggenweiler H-M, Sirrenberg C, Buchstaller H-P. 1,3-Dihydroisoindole derivatives as HSP90 inhibitors, their preparation, pharmaceutical compositions, and use in therapy. DE102007041116; 2009
103. Mantegani S, Brasca MG, Casuscelli F, et al. Preparation of bicyclic pyrazole and isoxazole derivatives as antitumor and antineurodegenerative agents and as agents for treating other diseases mediated by HSP90 protein. WO2010060854; 2010
104. Brasca MG, Casale E, Ferguson R, et al. Preparation of resorcinol derivatives as HSP90 inhibitors. WO2010121963; 2010
105. Brasca MG, Mantegani S, Amboldi N, et al. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem 2013;21:7047-63
106. Massey AJ. ATPases as drug targets: insights from heat shock proteins 70 and J Med Chem 2010;53:7280-6
107. Williamson DS, Borgognoni J, Clay A, et al. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J Med Chem 2009;52:1510-13
108. Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 2009;9:1337-51
109. Fewell SW, Smith CM, Lyon MA, et al. Small molecule modulators of endogenous and co-chaperonestimulated Hsp70 ATPase activity. J Biol Chem 2004;279:51131-40
110. Fewell SW, Day BW, Brodsky JL. Identification of an inhibitor of hsc70- mediated protein translocation and ATP hydrolysis. J Biol Chem 2001;276:910-14
111. Nadler SG, Eversole AC, Tepper MA, et al. Elucidating the mechanism of action of the immunosuppressant 15-deoxyspergualin. Ther Drug Monit 1995;17:700-3
112. Brodsky JL. Selectivity of the molecular chaperone-specific immunosuppressive agent 15- deoxyspergualin: modulation of Hsc70 ATPase activity without compromising DnaJ chaperone interactions. Biochem Pharmacol 1999;57:877-80
113. Jinwal UK, Miyata Y, Koren J III, et al. Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci 2009;29:12079-88
114. Kawakami M, Koya K, Ukai T, et al. Structure-activity of novel rhodacyanine dyes as antitumor agents. J Med Chem 1998;41:130-42
115. Kawakami M, Koya K, Ukai T, et al. Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity. J Med Chem 1997;40:3151-60
116. Wadhwa R, Sugihara T, Yoshida A, et al. Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function. Cancer Res 2000;60:6818-21
117. Chang L, Miyata Y, Ung PM, et al. Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol 2011;18:210-21
118. Rousaki A, Miyata Y, Jinwal UK, et al. Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones. J Mol Biol 2011;411:614-32
119. Shin I-J, Lee M-R, Williams D. Preparation of imidazoles (apoptazoles) as inducers of apoptosis. WO2008105565; 2008
120. Williams DR, Ko SK, Park S, et al. An apoptosis-inducing small molecule that binds to heat shock protein 70. Angew Chem Int Ed Engl 2008;47:7466-9
121. Cho HJ, Gee HY, Baek KH, et al. A small molecule that binds to an ATPase domain of Hsc70 promotes membrane trafficking of mutant cystic fibrosis transmembrane conductance regulator. J Am Chem Soc 2011;133:20267-76
122. Garrido C, Colas P, Bickle M, et al. New polypeptides binding to HSP70 ATPase domain and uses in cancer therapy. WO2009043942; 2009
123. Peptide inhibitors of heat shock protein 70 as inducers of apoptosis in cancer therapy. EP2050758; 2009
124. Rérole AL, Gobbo J, De Thonel A, et al. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res 2011;71:484-95
125. Cociancich S, Dupont A, Hegy G, et al. Novel inducible antibacterial peptides from a hemipteran insect, the sapsucking bug Pyrrhocoris apterus. Biochem J 1994;300:567-75
126. Sturgess MA, Kotch F. Preparation of small molecule and peptide DnaK inhibitors for treating bacterial infections. US20100087466; 2010
127. George DL, Leu JI-J, Murphy M. Screening methods for identifying HSP70/DNAK modulators and uses thereof in treatment of cancer. US20110189125; 2011
128. George DL, Leu JI-J, Murphy M. Modulators of HSP70/DnaK function, particularly 2- phenylethynesulfonamide (PES) derivatives, for use in potentiating the anticancer and antibacterial effects. WO2010033771; 2010
129. Strom E, Sathe S, Komarov PG, et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol 2006;2:474-9
130. Leu JI, Pimkina J, Frank A, et al. A small molecule inhibitor of inducible heat shock protein 70. Mol Cell 2009;36:15-27
131. Leu JI, Pimkina J, Pandey P, et al. HSP70 inhibition by the small-molecule 2-phenylethynesulfonamide impairs protein clearance pathways in tumor cells. Mol Cancer Res 2011;9:936-47
132. Balaburski GM, Leu JI, Beeharry N, et al. A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res 2013;11:219-29
133. Chiosis G, Taldone T, Rodina A, et al. Pyrimidine-based heat shock protein binding compounds, compositions, and methods for making and using same. WO2011022440; 2011
134. Rodina A, Patel PD, Kang Y, et al. Identification of an allosteric pocket on human hsp70 reveals a mode of inhibition of this therapeutically important protein. Chem Biol 2013;20:1469-80
135. Patel PD, Yan P, Seidler PM, et al. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nat Chem Biol 2013;9:677-84