- Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines
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Molecular chaperone heat shock protein 90 (Hsp90) is an important target in cancer and neurodegenerative diseases, and has rapidly become the focus of several drug discovery efforts. Among small molecule Hsp90 inhibitors with clinical applicability are de
- Tao, Hui,Kang, Yanlong,Taldone, Tony,Chiosis, Gabriela
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experimental part
p. 415 - 417
(2011/02/28)
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- SULFAMOYL-CONTAINING DERIVATIVES AND USES THEREOF
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Sulfamoyl-containing compounds are disclosed, having utility as inhibitors of disease-related targets, such as Heat Shock Protein 90 (HSP90), and which are useful for treating disorders, e.g., proliferative disorders, including HSP90-mediated disorders. Methods for preparing and using the disclosed compounds are also described.
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Page/Page column 20
(2008/06/13)
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- Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90
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Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and, thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. The study identifies water soluble derivatives (> 5 mM in PBS pH 7.4) of nanomolar potency (IC50 ~ 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenografted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors.
- He, Huazhong,Zatorska, Danuta,Kim, Joungnam,Aguirre, Julia,Llauger, Laura,She, Yuhong,Wu, Nian,Immormino, Robert M.,Gewirth, Daniel T.,Chiosis, Gabriela
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p. 381 - 390
(2007/10/03)
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- Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures
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Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold
- Dymock, Brian,Barril, Xavier,Beswick, Mandy,Collier, Adam,Davies, Nicholas,Drysdale, Martin,Fink, Alexandra,Fromont, Christophe,Hubbard, Roderick E.,Massey, Andrew,Surgenor, Allan,Wright, Lisa
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p. 325 - 328
(2007/10/03)
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