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| http://purl.uniprot.org/citations/23418523 | http://www.w3.org/2000/01/rdf-schema#comment | "Heat shock protein 90 (HSP90) is involved in the regulation of diverse biological processes such as cell signaling, proliferation and survival, and has been recently recognized as a potential target for cancer therapy. Ganetespib is a potent ATP competitive inhibitor of HSP90. Ganetespib downregulated the expression of multiple signal transducing molecules including EGFR, IGF-1R, c-Met, Akt, B-RAF and C-RAF, resulting in pronounced decrease in phosphorylation of Akt and Erk1/2 in a panel of five cutaneous melanoma cell lines including those harboring B-RAF and N-RAS mutations. Ganetespib exhibited potent antiproliferative activity on all five of these cell lines, with IC50 values between 37.5 and 84 nM. Importantly, Ganetespib is active on B-RAF mutated melanoma cells that have acquired resistance to B-RAF inhibition. Ganetespib induced apoptosis and cell cycle arrest at G1 and/or G2/M phase. Ganetespib induced cell cycle arrest was accompanied by altered expression of cyclin-dependent kinase inhibitor (CDKI) p21(Cip1) and p27(Kip1), cyclins B1, D1 and E, and/or cyclin-dependent kinases 1, 2 and 4. HSP90 is functionally important for melanoma cells and HSP90 inhibitors such as ganetespib could potentially be effective therapeutics for melanoma with various genetic mutations and acquired resistance to B-RAF inhibition."xsd:string |
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| http://purl.uniprot.org/citations/23418523 | http://purl.uniprot.org/core/author | "Wu X."xsd:string |
| http://purl.uniprot.org/citations/23418523 | http://purl.uniprot.org/core/author | "Hodi F.S."xsd:string |
| http://purl.uniprot.org/citations/23418523 | http://purl.uniprot.org/core/author | "Marmarelis M.E."xsd:string |
| http://purl.uniprot.org/citations/23418523 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
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| http://purl.uniprot.org/citations/23418523 | http://purl.uniprot.org/core/title | "Activity of the heat shock protein 90 inhibitor ganetespib in melanoma."xsd:string |
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