{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Amatya E"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["e202400418"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11649481"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(24)"],"pubmed_abstract":["Heat Shock Protein 90 (Hsp90) is responsible for the proper folding and maturation of ~400 client protein substrates, many of which are directly associated with the ten hallmarks of cancer. Hsp90 is a great target for cancer therapy including melanoma, since Hsp90 inhibition can disrupt multiple oncogenic pathways simultaneously. In this study, we report the synthesis and anti-proliferative activity manifested by a series of Hsp90 C-terminal inhibitors against mutant BRAF and wild-type BRAF melanoma cells. Furthermore, we explored structure-activity relationships (SAR) for the amide moiety of 6 (B1), a novel Hsp90C-terminal inhibitor via introduction of amide bioisosteres. Compound 6 displayed an IC<sub>50</sub> of 1.01 μM, 0.782 μM, 0.607 μM and 1.413 μM against SKMel173, SKMel103, SKMel1"],"journal":["ChemMedChem"],"pubmed_title":["The Investigation of Hsp90C-Terminal Inhibitors Containing Amide Bioisosteres."],"pmcid":["PMC11649481"],"funding_grant_id":["R01 CA216919","CA270147","R01 CA270147"],"pubmed_authors":["McNamara K","Amatya E","Cohen MS","Long R","Blagg BSJ","Subramanian C"],"additional_accession":[]},"is_claimable":false,"name":"The Investigation of Hsp90C-Terminal Inhibitors Containing Amide Bioisosteres.","description":"Heat Shock Protein 90 (Hsp90) is responsible for the proper folding and maturation of ~400 client protein substrates, many of which are directly associated with the ten hallmarks of cancer. Hsp90 is a great target for cancer therapy including melanoma, since Hsp90 inhibition can disrupt multiple oncogenic pathways simultaneously. In this study, we report the synthesis and anti-proliferative activity manifested by a series of Hsp90 C-terminal inhibitors against mutant BRAF and wild-type BRAF melanoma cells. Furthermore, we explored structure-activity relationships (SAR) for the amide moiety of 6 (B1), a novel Hsp90C-terminal inhibitor via introduction of amide bioisosteres. Compound 6 displayed an IC<sub>50</sub> of 1.01 μM, 0.782 μM, 0.607 μM and 1.413 μM against SKMel173, SKMel103, SKMel1","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-07T05:00:07.01Z","creation":"2026-06-07T03:06:29.81Z"},"accession":"S-EPMC11649481","cross_references":{"pubmed":["39153203"],"doi":["10.1002/cmdc.202400418"]}}