SR 1078

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SR1078 是视黄酸受体相关孤儿受体 (ROR)α/γ 的激动剂。

SR-1078 is a selective agonist of RORα and RORγ that stimulates ROR transcriptional activity in HEK293 cell reporter assays at concentrations as low as 2 μM without effect at the related liver X receptors and farnesoid X receptors. SR1078 modulates the conformation of RORγ in a biochemical assay and activates RORα and RORγ driven transcription. SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORα and RORγ. SR1078 can be utilized as a chemical tool to probe the function of these receptors both in vitro and in vivo.

SR1078 is a synthetic RORα/RORγ ligand. SR1078 modulates the conformation of RORγ in a biochemical assay and activates RORα and RORγ driven transcription. Furthermore, SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORα and RORγ. In a cell-based chimeric receptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR1078 significantly inhibits the constitutive transactivation activity of RORα and RORγ, but has no effect on the activity of FXR, LXRα and LXRβ. In a RORα cotransfection assay, treatment of cells with SR1078 (10 μM) results in a significant increase in transcription. Similarly, in the RORγ cotransfection assay, SR1078 treatment results in a stimulation of RORγ-dependent transcription activity.?SR1078 (2-10 μM; 24 hours) shows a dose-dependent increase in expression of A2BP1, CYP19A1, NLGN1, and IPTR1 in SH-SY5Y cells. EC50’s are in the range of 3-5 μM.

The pharmacokinetic properties of SR1078 are examined in mice and noted significant exposure. Plasma concentrations reach 3.6 μM 1h after a 10 mg/kg i.p. injection of SR1078 and sustained levels of above 800 nM even 8h after the single injection. These levels are sufficient to perform a proof-of-principle experiment to determine if SR1078 treatment would stimulate ROR target gene expression in an animal model. Mice are treated with SR1078 (10 mg/kg; i.p.) and 2h after the injection the livers are harvested and mRNA purified for assessment of G6Pase and FGF21 gene expression.T he expression of both FGF21 and G6Pase is significantly stimulated by SR1078 treatment vs. vehicle control.?SR1078 (10 mg/kg; i.p.) shows a significant 25% reduction in repetitive grooming behavior in the BTBR mice.

SR-1078 | SR 1078 | SR1078

GPCR/G Protein

Antibacterial

RORα|RORγ

Cancer

——

1246525-60-9

431.25

C17H10F9NO2

>98% (HPLC)

DMSO : 33.33 mg/mL 77.29 mM;

OC(c1ccc(NC(=O)c2ccc(cc2)C(F)(F)F)cc1)(C(F)(F)F)C(F)(F)F

N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-4-(trifluoromethyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years