The Hsp90 chaperone as a promising drug target

Current Opinion in Investigational Drugs

Volumn 2, Issue 11, 2001, Pages 1606-1610

  Piper, P W ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Antitumor; Chaperone; CP 127374; Geldanamycin; GMT 1; Heat shock protein; Hsp90; PI3K 2 GM; Radicicol

Indexed keywords

17 ALLYLAMINOGELDANAMYCIN; ADENOSINE DIPHOSPHATE; ADENOSINE TRIPHOSPHATE; ANSAMYCIN DERIVATIVE; ANTIBIOTIC AGENT; ANTIESTROGEN; CHAPERONE; CP 127374; DIMETHYL SULFOXIDE; ESTRADIOL; ESTROGEN; GELDANAMYCIN; GMT 1; HEAT SHOCK PROTEIN 90; HERBIMYCIN A; HYBRID PROTEIN; MACROLIDE; P13K 2 GM; PROTEIN INHIBITOR; RADICICOL; TAMOXIFEN; TESTOSTERONE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; BINDING KINETICS; CANCER; CATALYSIS; CELL CULTURE; CELL CYCLE; CLINICAL TRIAL; DRUG BINDING; DRUG DESIGN; DRUG INHIBITION; DRUG PROTEIN BINDING; DRUG SOLUBILITY; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TARGETING; EUKARYOTE; HUMAN; ISCHEMIA; MALARIA; NONHUMAN; ONCOLOGY; PROTEIN DEGRADATION; PROTEIN INDUCTION; REGULATORY MECHANISM; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; VIRUS INFECTION;

ANIMALS; ANTIBIOTICS, ANTIFUNGAL; ANTIBIOTICS, ANTINEOPLASTIC; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR CHAPERONES;

EID: 0035176758     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (42)

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2. Hsp90 as a capacitor for morphological evolution
3. Regulation of Hsp90 ATPase activity tetratricopeptide repeat (TPR)-domain co-chaperones
4. Polypeptide release by hsp90 involves ATP hydrolisis and is enhanced by the co-chaperone p23
5. Mutational analysis of Hsp90 function: Interactions with a steroid receptor and a protein kinase
6. Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest
7. Phenotypic change from transformed to normal induced by benzoquinoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus
8. Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol
9. Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90
10. Radicicol binds and inhibits mamalian ATP citrate lyase
11. Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones
12. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin
13. Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent
14. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone
15. ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo
16. In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis
17. Geldanamycin, a new antibiotic
18. Antifungal metabolites (monorden, monocillin IV, and cerebrosides) from Humicola fuscoatra traaen NRRL 22980, a mycoparasite of Aspergillus flauvs sclerotia
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23. Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90
24. Geldanamycin-stimulated destabilisation of mutated p53 is mediated by the proteasome in vivo
25. Transactivational and DNA binding abilities of endogenous p53 in p53 mutant cell lines
26. Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system
27. Disruption of the raf-1-Hsp90 molecular complex results in destabilisation of raf-1 and the loss of raf-1-ras association
28. Functional requirement of p23 and Hsp90 in telomerase complexes
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31. Antimalarial activity of radicicol, heptelidic acid and other fungal metabolites
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33. Induction of heat shock proteins by tyrosine kinase inhibitors in rat cardiomyocytes and myogenic cells confers protection against simulated ischemia
34. Dynamic activation of endothelial nitric oxide synthase by Hsp90
35. KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumour activity via selective depletion of Hsp90 binding signalling molecules
36. Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukemia cells through destabilisation of Bcr-Abl with Hsp90 complex
37. Repression of heat shock transcription factor HSF-1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1
38. Induction of a heat shock factor 1-dependent stress response and cytotoxic activity of hsp90-binding agents
39. Selective overexpression of mRNA coding for 90kDa stress protein in human ovarian cancer
40. Genotoxicity of streptonigrin: A review
41. Synthesis and biological evaluation of geldanamycin-testosterone linked hybrids
42. Synthesis and evaluation of geldanamycin-estradiol hybrids