For research use only. Not for therapeutic Use.
DY131(GSK 9089) is a novel selective agonist of ERRβ and ERRγ; displays minimal activity at ERRα, ERα and ERβ at concentrations up to 30 μM.Dy131 is a selective ERRγ agonist, could potentiate the ERRγ-induced growth inhibition in LNCaP- ERRγ and DU145- ERRγ cells in a dose-dependent manner compared with respective parental cells. DY131 inhibited the growth of the ERα-positive endometrial cancer cells but promoted that of the ERα-negative cancer cells. DY131 had no effect on the structurally related receptors ERRα or the estrogen receptors alpha and beta (ERalpha/beta). DY131 appears to inhibit Smo signaling through a common binding site shared by previously reported Smo agonists and antagonists.
| Catalog Number | I005650 |
| CAS Number | 95167-41-2 |
| Synonyms | DY-131; GSK 9089; |
| Purity | ≥95% |
| Target | ERRγ |
| Solubility | 10 mM in DMSO |
| Storage | Store at -20°C |
| InChI | InChI=1S/C18H21N3O2/c1-3-21(4-2)16-9-5-14(6-10-16)13-19-20-18(23)15-7-11-17(22)12-8-15/h5-13,22H,3-4H2,1-2H3,(H,20,23)/b19-13+ |
| Reference | 1:Oncotarget. 2016 Jul 26;7(30):47201-47220. doi: 10.18632/oncotarget.9719. Antimitotic activity of DY131 and the estrogen-related receptor beta 2 (ERRβ2) splice variant in breast cancer.Heckler MM,Zeleke TZ,Divekar SD,Fernandez AI,Tiek DM,Woodrick J,Farzanegan A,Roy R,Üren A,Mueller SC,Riggins RB, PMID: 27363015 PMCID: PMC5216935 DOI: 10.18632/oncotarget.9719 </br><span>Abstract:</span> Breast cancer remains a leading cause of cancer-related death in women, and triple negative breast cancer (TNBC) lacks clinically actionable therapeutic targets. Death in mitosis is a tumor suppressive mechanism that occurs in cancer cells experiencing a defective M phase. The orphan estrogen-related receptor beta (ERRβ) is a key reprogramming factor in murine embryonic and induced pluripotent stem cells. In primates, ERRβ is alternatively spliced to produce several receptor isoforms. In cellular models of glioblastoma, short form (ERRβsf) and beta2 (ERRβ2) splice variants differentially regulate cell cycle progression in response to the synthetic agonist DY131, with ERRβ2 driving arrest in G2/M.The goals of the present study are to determine the cellular function(s) of ligand-activated ERRβ splice variants in breast cancer and evaluate the potential of DY131 to serve as an antimitotic agent, particularly in TNBC. DY131 inhibits growth in a diverse panel of breast cancer cell lines, causing cell death that involves the p38 stress kinase pathway and a bimodal cell cycle arrest. ERRβ2 facilitates the block in G2/M, and DY131 delays progression from prophase to anaphase. Finally, ERRβ2 localizes to centrosomes and DY131 causes mitotic spindle defects. Targeting ERRβ2 may therefore be a promising therapeutic strategy in breast cancer. |
