Development of small-molecule-based probes for the vitamin D receptor

2020 ◽  
Author(s):  
Tania Mutchie ◽  
Alexander Arnold
Keyword(s):  
Vitamin D ◽  
Small Molecule ◽  
Vitamin D Receptor

scholarly journals Targeting Vitamin-D receptor (VDR) by a small molecule antagonist MeTC7 inhibits PD-L1 but controls THMYCN neuroblastoma growth PD-L1 independently

2020 ◽  
Author(s):  
Rakesh K. Singh ◽  
KyuKwang Kim ◽  
Rachael B. Rowswell-Turner ◽  
Jeanne N. Hansen ◽  
Negar Khazan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cancer Cells ◽  
Small Molecule ◽  
Vitamin D Receptor ◽  
Surface Expression ◽  
Small Molecule Antagonist ◽  
Inflammatory Monocytes ◽  
Pancreatic Cancer Cells ◽  
Stat3 Phosphorylation

AbstractVitamin-D receptor (VDR) mRNA is enriched in malignant lung, ovarian and pancreatic tissues and showed poor prognoses. Calcitriol and stable or CRISPR-directed VDR upregulation increased PD-L1mRNA and protein expression in cancer cells in-vitro. A ChIP assay showed the binding of VDR with VDREPD-L1. Stattic, a STAT3 phosphorylation inhibitor blocked calcitriol or VDR overexpression induced PD-L1 upregulation. MeTC7, a VDR antagonist developed by us, reduced PD-L1 expression on macrophages, ovarian, lung, breast, and pancreatic cancer cells in-vitro. In radiotherapy inducible PD-L1 model of orthotopic MC38 murine colon cancer, MeTC7 decreased PD-L1 surface expression, suppressed inflammatory monocytes (IMs) population and increased intra-tumoral CD69+PD1+CD8+T-cells. Intriguingly, MeTC7 reduced TH-MYCN transgenic neuroblastoma tumor growth without affecting PD-L1 and tumor immune milieu. In summary, Vitamin-D/VDR drives PD-L1 expression on cancer cells via STAT-3. Inhibiting VDR exhibited anti-checkpoint effects in orthotopic colon tumors, whereas PDL1-independent and anti-VDR/MYCN effects controlled growth of transgenic neuroblastoma and xenografted tumors.SummaryVitamin-D/VDR induces PD-L1 expression on cancer cells via STAT-3; and targeting VDR by a novel small molecule antagonist MeTC7 exhibits both anti-PD-L1 and anti-VDR/MYCN effects in tumor models.

scholarly journals Development of small-molecule-based probes for the vitamin D receptor

2020 ◽  
Author(s):  
Tania Mutchie ◽  
Rodrigo Hernandez ◽  
Daniel Webb ◽  
Fernando Morales ◽  
Leggy Arnold
Keyword(s):  
Vitamin D ◽  
Small Molecule ◽  
Vitamin D Receptor

scholarly journals Discovery of the First Irreversible Small Molecule Inhibitors of the Interaction between the Vitamin D Receptor and Coactivators

2012 ◽  
Vol 55 (10) ◽  
pp. 4640-4651 ◽  
Author(s):  
Premchendar Nandhikonda ◽  
Wen Z. Lynt ◽  
Megan M. McCallum ◽  
Tahniyath Ara ◽  
Athena M. Baranowski ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Molecule ◽  
Vitamin D Receptor ◽  
Small Molecule Inhibitors

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis

2001 ◽  
Vol 28 (1) ◽  
pp. 89-93 ◽  
Author(s):  
J. R. Garcia-Lozano ◽  
M. F. Gonzalez-Escribano ◽  
A. Valenzuela ◽  
A. Garcia ◽  
A. Nunez-Roldan
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Early Onset

803: Interactions Between Ultraviolet Radiation and Polymorphisms in the Vitamin D Receptor Gene Mediate Prostate Cancer Susceptibility

2006 ◽  
Vol 175 (4S) ◽  
pp. 260-260
Author(s):  
Nicholas J. Rukin ◽  
Samuel J. Moon ◽  
Dhaval Bodiwala ◽  
Christopher J. Luscombe ◽  
Mark F. Saxby ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Ultraviolet Radiation ◽  
Vitamin D Receptor ◽  
Cancer Susceptibility ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Prostate Cancer Susceptibility

368: The Analysis of Vitamin D Receptor and Retinoid X Receptor in Renal Cell Carcinoma

2005 ◽  
Vol 173 (4S) ◽  
pp. 101-101
Author(s):  
Wataru Obara ◽  
Ryuichiro Konda ◽  
Tomoaki Fujioka
Keyword(s):  
Renal Cell Carcinoma ◽  
Vitamin D ◽  
Cell Carcinoma ◽  
Vitamin D Receptor ◽  
Renal Cell ◽  
Retinoid X Receptor

487: Vitamin D Receptor Gene Haplotypes and Prostate Cancer in Hispanic and Non-Hispanic White Men: Results from a Case-Control Genetic Association Study

2006 ◽  
Vol 175 (4S) ◽  
pp. 158-158
Author(s):  
Kathleen C. Torkko ◽  
Phuong Mai ◽  
Robin J. Leach ◽  
Betsy A. Higgins ◽  
Adrie Van Bokhoven ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Association Study ◽  
Vitamin D Receptor ◽  
Genetic Association Study ◽  
Receptor Gene ◽  
White Men ◽  
Case Control ◽  
Vitamin D Receptor Gene ◽  
Hispanic White
Sign in / Sign up

Export Citation Format

Share Document