Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 33, 2016, Pages E4801-E4809

  Yim, Kendrick H ^a   Prince, Thomas L ^a   Qu, Shiwei ^b   Bai, Fang ^c   Jennings, Patricia A ^b   Onuchic, José N ^c   Theodorakis, Emmanuel A ^a   Neckers, Leonard ^a,b  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c RICE UNIVERSITY   (United States)

Author keywords

Caged xanthone; Heat shock protein 90 ; Isoform specific inhibitor; Molecular chaperone; Molecular docking

Indexed keywords

DAP 19; GAMBOGIC ACID; GANETESPIB; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 90 INHIBITOR; HEAT SHOCK PROTEIN 90BETA; ISOPROTEIN; UNCLASSIFIED DRUG; HEAT SHOCK PROTEIN 90; HSP90AB1 PROTEIN, HUMAN; XANTHONE DERIVATIVE;

ARTICLE; DELETION MUTANT; DRUG BINDING SITE; DRUG PROTEIN BINDING; DRUG SELECTIVITY; MEDICINAL CHEMISTRY; MOLECULAR DOCKING; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMPUTER SIMULATION; HEK293 CELL LINE; HUMAN; METABOLISM; SITE DIRECTED MUTAGENESIS;

COMPUTER SIMULATION; HEK293 CELLS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MUTAGENESIS, SITE-DIRECTED; PROTEIN DOMAINS; PROTEIN ISOFORMS; XANTHONES;

EID: 84982108513     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1606655113     Document Type: Article

References (66)

1. Taipale M, Jarosz DF, Lindquist S (2010) HSP90 at the hub of protein homeostasis: Emerging mechanistic insights. Nat Rev Mol Cell Biol 11(7):515-528.
2. Krukenberg KA, Street TO, Lavery LA, Agard DA (2011) Conformational dynamics of the molecular chaperone Hsp90. Q Rev Biophys 44(2):229-255.
3. Miyata Y, Nakamoto H, Neckers L (2013) The therapeutic target Hsp90 and cancer hallmarks. Curr Pharm Des 19(3):347-365.
4. Zhao YH, et al. (2009) Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth. Oncogene 28(42):3689-3701.
5. Minet E, et al. (1999) Hypoxia-induced activation of HIF-1: Role of HIF-1α-Hsp90 interaction. FEBS Lett 460(2):251-256.
6. Neckers L, Workman P (2012) Hsp90 molecular chaperone inhibitors: Are we there yet? Clin Cancer Res 18(1):64-76.
7. Sreedhar AS, Kalmár E, Csermely P, Shen YF (2004) Hsp90 isoforms: Functions, expression and clinical importance. FEBS Lett 562(1-3):11-15.
8. Prince TL, et al. (2015) Client proteins and small molecule inhibitors display distinct binding preferences for constitutive and stress-induced HSP90 isoforms and their conformationally restricted mutants. PLoS One 10(10):0141786.
9. Patel PD, et al. (2013) Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nat Chem Biol 9(11):677-684.
10. Altieri DC (2013) Mitochondrial HSP90s and tumor cell metabolism. Autophagy 9(2): 244-245.
11. Zhu G, Lee AS (2015) Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol 230(7):1413-1420.
12. Panaretou B, et al. (2002) Activation of the ATPase activity of Hsp90 by the stressregulated cochaperone Aha1. Mol Cell 10(6):1307-1318.
13. Prodromou C, et al. (2000) The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N- Terminal domains. EMBO J 19(16):4383-4392.
14. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475(7356):324-332.
15. Sun L, Prince T, Manjarrez JR, Scroggins BT, Matts RL (2012) Characterization of the interaction of Aha1 with components of the Hsp90 chaperone machine and client proteins. Biochim Biophys Acta 1823(6):1092-1101.
16. Zhang H, Burrows F (2004) Targeting multiple signal transduction pathways through inhibition of Hsp90. J Mol Med (Berl) 82(8):488-499.
17. Whitesell L, Lindquist SL (2005) HSP90 and the chaperoning of cancer. Nat Rev Cancer 5(10):761-772.
18. Pearl LH, Prodromou C, Workman P (2008) The Hsp90 molecular chaperone: An open and shut case for treatment. Biochem J 410(3):439-453.
19. Ali MM, et al. (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440(7087):1013-1017.
20. Roe SM, et al. (2004) The mechanism of Hsp90 regulation by the protein kinasespecific cochaperone p50(cdc37). Cell 116(1):87-98.
21. Prodromou C, et al. (1997) Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90(1):65-75.
22. Chandarlapaty S, et al. (2008) SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res 14(1):240-248.
23. Ying W, et al. (2012) Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 11(2):475-484.
24. Hostein I, Robertson D, DiStefano F, Workman P, Clarke PA (2001) Inhibition of signal transduction by the Hsp90 inhibitor 17- Allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res 61(10):4003-4009.
25. Donnelly A, Blagg BS (2008) Novobiocin and additional inhibitors of the Hsp90 C- Terminal nucleotide-binding pocket. Curr Med Chem 15(26):2702-2717.
26. Anyika M, McMullen M, Forsberg LK, Dobrowsky RT, Blagg BS (2015) Development of noviomimetics as C- Terminal Hsp90 inhibitors. ACS Med Chem Lett 7(1):67-71.
27. Buckton LK, Wahyudi H, McAlpine SR (2016) The first report of direct inhibitors that target the C- Terminal MEEVD region on heat shock protein 90. Chem Commun (Camb) 52(3):501-504.
28. Garcia-Carbonero R, Carnero A, Paz-Ares L (2013) Inhibition of HSP90 molecular chaperones: Moving into the clinic. Lancet Oncol 14(9):e358-e369.
29. Hong DS, et al. (2013) Targeting the molecular chaperone heat shock protein 90 (HSP90): Lessons learned and future directions. Cancer Treat Rev 39(4):375-387.
30. Bhat R, Tummalapalli SR, Rotella DP (2014) Progress in the discovery and development of heat shock protein 90 (Hsp90) inhibitors. J Med Chem 57(21):8718-8728.
31. Duerfeldt AS, et al. (2012) Development of a Grp94 inhibitor. J Am Chem Soc 134(23): 9796-9804.
32. Muth A, et al. (2014) Development of radamide analogs as Grp94 inhibitors. Bioorg Med Chem 22(15):4083-4098.
33. Patel HJ, et al. (2015) Structure- Activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94. J Med Chem 58(9):3922-3943.
34. Liu W, et al. (2015) KU675, a concomitant heat-shock protein inhibitor of Hsp90 and Hsc70 that manifests isoform selectivity for Hsp90α in prostate cancer cells. Mol Pharmacol 88(1):121-130.
35. Chantarasriwong O, Batova A, Chavasiri W, Theodorakis EA (2010) Chemistry and biology of the caged Garcinia xanthones. Chemistry 16(33):9944-9962.
36. Chi Y, et al. (2013) An open-labeled, randomized, multicenter phase IIa study of gambogic acid injection for advanced malignant tumors. Chin Med J (Engl) 126(9): 1642-1646.
37. Gu H, et al. (2008) Gambogic acid mediates apoptosis as a p53 inducer through downregulation of mdm2 in wild- Type p53-expressing cancer cells. Mol Cancer Ther 7(10): 3298-3305.
38. Huang GM, Sun Y, Ge X, Wan X, Li CB (2015) Gambogic acid induces apoptosis and inhibits colorectal tumor growth via mitochondrial pathways. World J Gastroenterol 21(20):6194-6205.
39. Li C, et al. (2012) Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells. Biochem Cell Biol 90(6): 718-730.
40. Wang Y, et al. (2014) Methyl jasmonate sensitizes human bladder cancer cells to gambogic acid-induced apoptosis through down-regulation of EZH2 expression by miR-101. Br J Pharmacol 171(3):618-635.
41. Yi T, et al. (2008) Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling. Cancer Res 68(6): 1843-1850.
42. Yue Q, et al. (2016) Proteomic analysis revealed the important role of vimentin in human cervical carcinoma HeLa cells treated with gambogic acid. Mol Cell Proteomics 15(1):26-44.
43. Guizzunti G, Batova A, Chantarasriwong O, Dakanali M, Theodorakis EA (2012) Subcellular localization and activity of gambogic acid. ChemBioChem 13(8): 1191-1198.
44. Davenport J, et al. (2011) Gambogic acid, a natural product inhibitor of Hsp90. J Nat Prod 74(5):1085-1092.
45. Zhang L, et al. (2010) Gambogic acid inhibits Hsp90 and deregulates TNF-α/NF-κB in HeLa cells. Biochem Biophys Res Commun 403(3-4):282-287.
46. Matthews SB, et al. (2010) Characterization of a novel novobiocin analogue as a putative C- Terminal inhibitor of heat shock protein 90 in prostate cancer cells. Prostate 70(1):27-36.
47. Sidera K, Patsavoudi E (2014) HSP90 inhibitors: Current development and potential in cancer therapy. Recent Patents Anticancer Drug Discov 9(1):1-20.
48. Chen B, Piel WH, Gui L, Bruford E, Monteiro A (2005) The HSP90 family of genes in the human genome: Insights into their divergence and evolution. Genomics 86(6): 627-637.
49. Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB (1995) Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem 270(8):3574-3581.
50. Soldano KL, Jivan A, Nicchitta CV, Gewirth DT (2003) Structure of the N- Terminal domain of GRP94. Basis for ligand specificity and regulation. J Biol Chem 278(48): 48330-48338.
51. Matts RL, et al. (2011) A systematic protocol for the characterization of Hsp90 modulators. Bioorg Med Chem 19(1):684-692.
52. Elbel KM, et al. (2013) A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones. Org Biomol Chem 11(20):3341-3348.
53. Bai F, et al. (2015) The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer. Proc Natl Acad Sci USA 112(12):3698-3703.
54. Theodoraki MA, et al. (2015) Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening. Oncotarget 6(25):21255-21267.
55. Peterson LB, Eskew JD, Vielhauer GA, Blagg BSJ (2012) The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking. Mol Pharm 9(6): 1841-1846.
56. Hadden MK, Lubbers DJ, Blagg BS (2006) Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N- Terminal ATP binding site. Curr Top Med Chem 6(11): 1173-1182.
57. Matts RL, et al. (2011) Elucidation of the Hsp90 C- Terminal inhibitor binding site. ACS Chem Biol 6(8):800-807.
58. Chantarasriwong O, et al. (2009) Evaluation of the pharmacophoric motif of the caged Garcinia xanthones. Org Biomol Chem 7(23):4886-4894.
59. Tisdale EJ, Slobodov I, Theodorakis EA (2004) Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels-Alder/Claisen rearrangement. Proc Natl Acad Sci USA 101(33):12030-12035.
60. Bai F, et al. (2013) Free energy landscape for the binding process of Huperzine A to acetylcholinesterase. Proc Natl Acad Sci USA 110(11):4273-4278.
61. Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W (2013) Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27(3):221-234.
62. Lang PT, et al. (2009) DOCK 6: Combining techniques to model RNA-small molecule complexes. RNA 15(6):1219-1230.
63. Mills N (2006) ChemDraw Ultra 10.0 CambridgeSoft, 100 CambridgePark Drive, Cambridge, MA 02140. www.cambridgesoft.com. Commercial Price: $1910 for download, $2150 for CD-ROM; Academic Price: $710 for download, $800 for CD-ROM. J AmChem Soc 128(41):13649-13650.
64. Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity- A rapid access to atomic charges. Tetrahedron 36(22):3219-3228.
65. Hawkins GD, Cramer CJ, Truhlar DG (1996) Parametrized models of aqueous free energies of solvation based on pairwise descreening of solute atomic charges from a dielectric medium. J Phys Chem 100(51):19824-19839.
66. Zou X, Sun Y, Kuntz ID (1999) Inclusion of solvation in ligand binding free energy calculations using the generalized-born model. J Am Chem Soc 121(35):8033-8043.