SR3335

"目录号: HY-14413

Metabolic Enzyme/Protease-

SR3335 是一种选择性的RORα配体，直接结合到 RORα (Ki220 nM) 而非其他 RORs，在细胞实验中，用作选择性的 RORα反向激动剂。

ROR

相关产品

SR1078-SR1001-GSK2981278-ROR gamma-t-IN-1-LYC-55716-

生物活性

Description

SR3335 is a selectiveRORαsynthetic ligand, directly binds to RORα (Ki220 nM) but not other RORs, and functions as a selective partial inverse agonist of RORα in cell-based assays.

IC50& Target

Ki: 220 nM (RORα)[1]

In Vitro

SR3335 is a selective RORα partial inverse agonist. In a biochemical radioligand binding assay using [3H]25-hydroxycholesterol as a label it is clear that unlabeled SR3335 dose-dependently competes for binding to the RORα LBD. The Kiis calculated as 220 nM using the Cheng-Prusoff equation. In a cell-based chimeric receptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR3335 significantly inhibits the constitutive transactivation activity of RORα (IC50=480 nM)(partial inverse agonist activity), but has no effect on the activity of LXRα and RORγ[1].

In Vivo

Pharmacokinetic studies indicate that SR3335 displays reasonable exposure following an i.p. injection into mice. The ability of SR3335 is assessed to suppress gluconeogenesis using a diet induced obesity (DIO) mouse model where the mice where treated with 15 mg/kg b.i.d., i.p. for 6-days followed by a pyruvate tolerance test. SR3335 treated mice displays lower plasma glucose levels following the pyruvate challenge consistent with suppression of gluconeogenesis. Importantly, mice treated with SR3335 displayed no difference in body weight or food intake after 7-days of treatment with SR3335[1].

References

[1].Kumar N, et al. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist. ACS Chem Biol. 2011 Mar 18;6(3):218-22.