| ID | 65961 |
| FullText URL | |
| Author |
Khazan, Negar
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Kim, Kyu Kwang
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Hansen, Jeanne N.
Department of Pediatrics, University of Rochester Medical Center
Singh, Niloy A.
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Moore, Taylor
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Snyder, Cameron W. A.
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Pandita, Ravina
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Strawderman, Myla
Department of Biostatistics and Computational Biology, University of Rochester Medical Center
Fujihara, Michiko
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takamura, Yuta
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jian, Ye
Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center
Battaglia, Nicholas
Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center
Yano, Naohiro
Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University
Teramoto, Yuki
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center
Arnold, Leggy A.
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee
Hopson, Russell
Department of Chemistry, Brown University
Kishor, Keshav
Department of Chemistry, Birla Institute of Technology
Nayak, Sneha
Department of Chemistry, Birla Institute of Technology
Ojha, Debasmita
Department of Chemistry, Birla Institute of Technology
Sharon, Ashoke
Department of Chemistry, Birla Institute of Technology
Ashton, John M.
Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center
Wang, Jian
Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University
Milano, Michael T.
Department of Radiation Oncology, University of Rochester Medical Center
Miyamoto, Hiroshi
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center
Linehan, David C.
Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center
Gerber, Scott A.
Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center
Kawar, Nada
Center for Breast Health and Gynecologic Oncology, Mercy Medical Center
Singh, Ajay P.
Rutgers, The State University of New Jersey
Tabdanov, Erdem D.
CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University
Dokholyan, Nikolay V.
Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University
Kakuta, Hiroki
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Jurutka, Peter W.
School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center
Schor, Nina F.
Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center
Rowswell-Turner, Rachael B.
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Singh, Rakesh K.
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
Moore, Richard G.
Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center
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| Abstract | Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize.
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| Published Date | 2022-04-11
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| Publication Title |
Journal of Medicinal Chemistry
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| Volume | volume65
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| Issue | issue8
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| Publisher | American Chemical Society (ACS)
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| Start Page | 6039
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| End Page | 6055
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| ISSN | 0022-2623
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| NCID | AA00702411
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| Content Type |
Journal Article
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| language |
English
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| OAI-PMH Set |
岡山大学
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| Copyright Holders | © 2022 The Authors.
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| File Version | publisher
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| PubMed ID | |
| DOI | |
| Web of Science KeyUT | |
| Related Url | isVersionOf https://doi.org/10.1021/acs.jmedchem.1c01878
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| License | https://creativecommons.org/licenses/by/4.0/
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| Citation | J. Med. Chem. 2022, 65, 6039−6055
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