2vci: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2vci.jpg|left|200px]] | [[Image:2vci.jpg|left|200px]] | ||
'''4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER''' | {{Structure | ||
|PDB= 2vci |SIZE=350|CAPTION= <scene name='initialview01'>2vci</scene>, resolution 2.00Å | |||
|SITE= <scene name='pdbsite=AC1:2gj+Binding+Site+For+Chain+A'>AC1</scene> | |||
|LIGAND= <scene name='pdbligand=2GJ:'>2GJ</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2VCI is a [ | 2VCI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VCI OCA]. | ||
==Reference== | ==Reference== | ||
4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer., Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ, Dymock B, Eccles SA, Finch H, Fink A, Hayes A, Howes R, Hubbard RE, James K, Jordan AM, Lockie A, Martins V, Massey A, Matthews TP, McDonald E, Northfield CJ, Pearl LH, Prodromou C, Ray S, Raynaud FI, Roughley SD, Sharp SY, Surgenor A, Walmsley DL, Webb P, Wood M, Workman P, Wright L, J Med Chem. 2008 Jan 24;51(2):196-218. Epub 2007 Nov 20. PMID:[http:// | 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer., Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ, Dymock B, Eccles SA, Finch H, Fink A, Hayes A, Howes R, Hubbard RE, James K, Jordan AM, Lockie A, Martins V, Massey A, Matthews TP, McDonald E, Northfield CJ, Pearl LH, Prodromou C, Ray S, Raynaud FI, Roughley SD, Sharp SY, Surgenor A, Walmsley DL, Webb P, Wood M, Workman P, Wright L, J Med Chem. 2008 Jan 24;51(2):196-218. Epub 2007 Nov 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18020435 18020435] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 59: | Line 68: | ||
[[Category: stress response]] | [[Category: stress response]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:45:28 2008'' | ||
Revision as of 19:45, 20 March 2008
| |||||||
| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER
OverviewOverview
Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by approximately 50%.
About this StructureAbout this Structure
2VCI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer., Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ, Dymock B, Eccles SA, Finch H, Fink A, Hayes A, Howes R, Hubbard RE, James K, Jordan AM, Lockie A, Martins V, Massey A, Matthews TP, McDonald E, Northfield CJ, Pearl LH, Prodromou C, Ray S, Raynaud FI, Roughley SD, Sharp SY, Surgenor A, Walmsley DL, Webb P, Wood M, Workman P, Wright L, J Med Chem. 2008 Jan 24;51(2):196-218. Epub 2007 Nov 20. PMID:18020435
Page seeded by OCA on Thu Mar 20 18:45:28 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Aherne, W.
- Barril, X.
- Borgognoni, J.
- Boxal, K.
- Brough, P A.
- Cansfield, J E.
- Cheung, K M.
- Collins, I.
- Davies, N G.M.
- Drysdale, M J.
- Dymock, B.
- Eccles, S A.
- Finch, H.
- Fink, A.
- Hayes, A.
- Howes, R.
- Hubbard, R E.
- James, K.
- Jordan, A M.
- Lockie, A.
- Martins, V.
- Massey, A.
- Matthews, T P.
- Mcdonald, E.
- Northfield, C J.
- Pearl, L H.
- Prodromou, C.
- Ray, S.
- Raynaud, F I.
- Roughley, S D.
- Sharp, S Y.
- Surgenor, A.
- Walmsley, D L.
- Webb, P.
- Wood, M.
- Workman, P.
- Wright, L.
- 2GJ
- Alternative splicing
- Atp-binding
- Chaperone
- Cytoplasm
- Nucleotide-binding
- Phosphorylation
- Stress response