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Purine-scaffold Hsp90 inhibitors.

ABSTRACT: Hsp90 is a molecular chaperone with important roles in regulating the function of several proteins with potential pathogenic activity. Because many of these proteins are involved in cancer and neurodegenerative promoting pathways, Hsp90 has emerged as an attractive therapeutic target in these diseases. Molecules that bind to the N-terminal nucleotide pocket of Hsp90 inhibit its activity, and consequently, disrupt client protein function. A number of these inhibitors from several chemical classes are now known, and some are already in clinical trials. This review focuses on the purine class of Hsp90 inhibitors, their discovery through rational design, and on efforts aimed towards their optimization and development into clinically viable drugs for the treatment of cancer. Their potential towards neurodegenerative diseases will also be touched upon.

SUBMITTER: Taldone T

PROVIDER: S-EPMC4699796 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Purine-scaffold Hsp90 inhibitors.

Taldone Tony T Chiosis Gabriela G

Current topics in medicinal chemistry 20090101 15

Hsp90 is a molecular chaperone with important roles in regulating the function of several proteins with potential pathogenic activity. Because many of these proteins are involved in cancer and neurodegenerative promoting pathways, Hsp90 has emerged as an attractive therapeutic target in these diseases. Molecules that bind to the N-terminal nucleotide pocket of Hsp90 inhibit its activity, and consequently, disrupt client protein function. A number of these inhibitors from several chemical classes ...[more]

PMID: 19860732

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The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining.

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| S-EPMC5110220 | biostudies-other

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