95167-41-2

Basic information

• Product Name: DY131
• Synonyms: GSK 9089;DY131(GSK 9089);4-Hydroxybenzoic acid 2-[[4-(diethylamino)phenyl]methylene]hydrazide;N'-(4-DIETHYLAMINOBENZYLIDENE)-4-HYDROXYBENZOYLHYDRAZIDE;N-(4-(DIETHYLAMINOBENZYLIDENYL))-N'-(4-HYDROXYBENZOYL)-HYDRAZINE;GSK4716;GW4716;GW574716
• CAS NO: 95167-41-2
• Molecular Formula: C₁₈H₂₁N₃O₂
• Molecular Weight: 311.38
• Product Categories: Intracellular receptor;Novel selective agonist at estrogen-related receptors ERRβ and ERRγ.;Inhibitors
• Mol File: 95167-41-2.mol

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: yellow/solid
• Density: 1.11g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥14 mg/mL
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: DY131(CAS DataBase Reference)
• NIST Chemistry Reference: DY131(95167-41-2)
• EPA Substance Registry System: DY131(95167-41-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• Hazardous Substances Data: 95167-41-2(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
DY131 is used as an antiproliferative agent for prostate cancer cells, inhibiting their growth and proliferation.
Used in Hormone Production and Cell Fusion:
DY131 is used as a promoter of hormone production and cell fusion in cytotrophoblasts, playing a role in the development and function of the placenta.
Used in Breast Cancer Treatment:
DY131 is used as an antimitotic agent in breast cancer cells, arresting cells in the G2/M phase and causing mitotic spindle defects, which can lead to cell cycle arrest and inhibition of tumor growth.
Used in Bone Health:
DY131 is used as an inhibitor of osteoclastogenesis and protector against inflammatory bone loss induced by LPS in vivo, potentially contributing to the maintenance of bone health and prevention of bone-related complications in certain conditions.

Biological Activity

Novel selective agonist at estrogen-related receptors ERR β and ERR γ . Displays minimal activity at ERR α , ER α and ER β at concentrations up to 30 μ M.

in vitro

dy131 was evaluated for its selectivity and efficacy in modulating the transcriptional activity of errα/β/γ and erβ/γ. cv-1 cells were transfected with reporter constructs or expression vectors and the fold activation of the reporter construct was determined at different concentrations of dy131. dy131 was found to be not able to activate the reporter construct or errα at any of the tested concentrations. in contrast, dy131 led to three- to fourfold activation of errβ at concentrations of 10-30 μm. activity on errγ was more pronounced with five-fold activation at 3 μm and maximal 6.6-fold activity observed at 30 μm. thus, dy131 was an selective errβ/γ ligand displaying preferential selectivity for errγ at lower concentrations [1].

References

1) Yu and Forman (2005),?Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma; Bioorg. Med. Chem. Lett.,?15?1311 2) Yu?et al.?(2008),?Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21 (WAF1/CIP1) induction and as a potential therapeutic target in prostate cancer; Oncogene,?27?3313 3) Poidatz?et al. (2015),?Trophoblast syncytialisation necessitates mitochondrial function through estrogen-related receptor-τ; Mol. Hum. Reprod.,?21?206 4) Heckler?et al.?(2016),?Antimitotic activity of DY131 and the estrogen-related receptor beta 2 (ERR?2) splice variant in breast cancer; Oncotarget,?7?47201 5) Kim?et al.?(2019),?Estrogen-related receptor τ negatively regulates osteoclastogenesis and protects against inflammatory bone loss; J. Cell Physiol.,?234?1659

Upstream product

• 5351-23-5 4-hydroxybenzoic acid hydrazide 
• 120-21-8 4-Diethylaminobenzaldehyde 
• 123-08-0 4-hydroxy-benzaldehyde 
• 3290-99-1 4-methoxybenzoic acid hydrazide 
• 99-96-7 4-hydroxy-benzoic acid 
• 99-76-3 methyl 4-hydroxylbenzoate 

Relevant articles and documents

Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRβ and ERRγ

The first small molecule agonists of the estrogen-related receptors have been identified. GSK4716 (3) and GSK9089 (4) show binding to ERRγ with remarkable selectivity over the classical estrogen receptors. Notably, in cell-based reporter assays, 3 mimics

Identification of an agonist ligand for estrogen-related receptors ERRβ/γ

In order to develop agonist ligands that are specific for the estrogen-related receptors ERRβ/γ, a hydrazone with a 4-hydroxy group at one phenyl ring and a 4-diethylamino moiety at the other phenyl ring was synthesized. We demonstrate that compound 3 (DY131; N′-{(1E)-[4- (diethylamino)phenyl]methylene}-4-hydroxybenzohydrazide) effectively and selectively activates ERRβ/γ. DY131 had no effect on the structurally related receptors ERRα or the estrogen receptors α and β (ERα/β). This work defines a convenient synthesis for a novel and selective pharmacologic tool that can be used to elucidate the biological activities of ERRβ/γ.

Design, synthesis, and antimicrobial evaluation of some nifuroxazide analogs against nosocomial infection

A series of 10 p-substitutedbenzoylmethylene hydrazide derivatives 4a-j were synthesized by protecting carboxylic group of 4-hydroxybenzoic acid using methanol and sulfuric acid than reacting it with hydrazide to form 4-hydroxybenzohydrazide followed by reacting with a variety of aldehydes and evaluated for their activity against nosocomial infection. All the synthesized compounds were characterized by Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), and mass spectral data. The in vitro antimicrobial potential of synthesized compounds was estimated against prominent strains of nosocomial pathogens (Staphylococcus aureus, Escherichia coli, and Aspergillus niger). The antimicrobial evaluation revealed compounds 4b, 4c, 4d, 4e, 4f, and 4j to be the most active compounds of the series with IC50 value for antibacterial in the range 0.39 to 0.75 μM/mL. Furthermore, the in vitro cytotoxic potential of the compounds was appraised by hemolytic assay. The results showed that some of the synthesized compounds exhibited marked activity.

(E)-N′-(4-Chlorobenzylidene)-,(E)-N′-(4-bromobenzylidene)- and (E)-N′-[4-(diethylamino)benzylidene]-derivatives of 4- hydroxybenzohydrazide

The 4-chloro- [C14H11ClN2O2, (I)], 4-bromo- [C14H10BrN2O2, (II)] and 4-diethyl-amino- [C18H21N3O2, (III)] derivatives of benzyl-idene-4-hy-droxy-benzo-hydrazide, all crystallize in the same space group (P21/c), (I) and (II) also being isomorphous. In all three compounds, the conformation about the C=N bond is E. The molecules of (I) and (II) are relatively planar, with dihedral angles between the two benzene rings of 5.75 (12) and 9.81 (17)°, respectively. In (III), however, the same angle is 77.27 (9)°. In the crystal structures of (I) and (II), two-dimensional slab-like networks extending in the a and c directions are formed via N - H...O and O - H...O hydrogen bonds. The molecules stack head-to-tail via π-π interactions involving the aromatic rings [centroid-centroid distance = 3.7622 (14) A in (I) and 3.8021 (19) A in (II)]. In (III), undulating two-dimensional networks extending in the b and c directions are formed via N - H...O and O - H...O hydrogen bonds. The molecules stack head-to-head via π-π interactions involving inversion-related benzene rings [cen-troid-centroid distances = 3.6977 (12) and 3.8368 (11) A].

Ligands for estrogen related receptors and methods for synthesis of said ligands

Estrogen-Related Receptor (ERR) modulating compounds and methods for synthesis of said compounds are described.