{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":53,"searchCount":0},"additional":{"submitter":["Xu YM"],"funding":["Arizona Biomedical Research Commission","Intramural NIH HHS","College of Agriculture and Life Sciences, University of Arizona","National Cancer Institute"],"pagination":["3039-3051"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6986374"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["60(7)"],"pubmed_abstract":["Renal cell carcinoma (RCC) is a cancer with poor prognosis, and the 5-year survival rate of patients with metastatic RCC is 5-10%. Consequently, treatment of metastatic RCC represents an unmet clinical need. Screening of a 50 000-member library of natural and synthetic compounds for sensitizers of RCC cells to TRAIL-mediated apoptosis led to identification of the 17β-hydroxywithanolide (17-BHW), withanolide E (1), as a promising lead. To explore structure-activity relationships, we obtained natural and semisynthetic withanolides 1, 2a, 2c, and 3-36 and compared their ability to sensitize TRAIL-mediated apoptosis in a panel of renal carcinoma cells. Our findings revealed that 17-BHWs with a α-oriented side chain are superior to known TRAIL-sensitizing withanolides belonging to withaferin A class with a β-oriented side chain and demonstrated that the 17-BHW scaffold can be modified to enhance sensitization of RCCs to TRAIL-mediated apoptosis, thereby assisting development of natural-product-inspired drugs to treat metastatic RCC."],"journal":["Journal of medicinal chemistry"],"pubmed_title":["17β-Hydroxywithanolides as Sensitizers of Renal Carcinoma Cells to Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) Mediated Apoptosis: Structure-Activity Relationships."],"pmcid":["PMC6986374"],"funding_grant_id":["HHSN26120080001E","Z01 BC010012"],"pubmed_authors":["Sayers TJ","Henrich CJ","Tewary P","Xu YM","Gunatilaka AA","Brooks AD","Wijeratne EM"],"view_count":["53"],"additional_accession":[]},"is_claimable":false,"name":"17β-Hydroxywithanolides as Sensitizers of Renal Carcinoma Cells to Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) Mediated Apoptosis: Structure-Activity Relationships.","description":"Renal cell carcinoma (RCC) is a cancer with poor prognosis, and the 5-year survival rate of patients with metastatic RCC is 5-10%. Consequently, treatment of metastatic RCC represents an unmet clinical need. Screening of a 50 000-member library of natural and synthetic compounds for sensitizers of RCC cells to TRAIL-mediated apoptosis led to identification of the 17β-hydroxywithanolide (17-BHW), withanolide E (1), as a promising lead. To explore structure-activity relationships, we obtained natural and semisynthetic withanolides 1, 2a, 2c, and 3-36 and compared their ability to sensitize TRAIL-mediated apoptosis in a panel of renal carcinoma cells. Our findings revealed that 17-BHWs with a α-oriented side chain are superior to known TRAIL-sensitizing withanolides belonging to withaferin A class with a β-oriented side chain and demonstrated that the 17-BHW scaffold can be modified to enhance sensitization of RCCs to TRAIL-mediated apoptosis, thereby assisting development of natural-product-inspired drugs to treat metastatic RCC.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Apr","modification":"2024-11-10T03:29:09.124Z","creation":"2020-10-29T16:06:22Z"},"accession":"S-EPMC6986374","cross_references":{"pubmed":["28257574"],"doi":["10.1021/acs.jmedchem.7b00069"]}}