For research use only. Not for therapeutic Use.
SR3335 (CAT: I003022) is a synthetic ligand that selectively targets the retinoic acid receptor-related orphan receptor alpha (RORα). It specifically binds to RORα and acts as a partial inverse agonist, modulating its activity. In cell-based assays, SR3335 has shown selectivity towards RORα and does not significantly interact with other ROR receptors. By targeting RORα, SR3335 has the potential to influence various cellular processes regulated by this receptor, making it a valuable tool for studying RORα-related pathways and developing therapeutic interventions for diseases associated with RORα dysregulation.
| Catalog Number | I003022 |
| CAS Number | 293753-05-6 |
| Synonyms | N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]thiophene-2-sulfonamide |
| Molecular Formula | C13H9F6NO3S2 |
| Purity | ≥95% |
| Target | ROR |
| Solubility | 10 mM in DMSO |
| Storage | Store at -20°C |
| IUPAC Name | N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]thiophene-2-sulfonamide |
| InChI | InChI=1S/C13H9F6NO3S2/c14-12(15,16)11(21,13(17,18)19)8-3-5-9(6-4-8)20-25(22,23)10-2-1-7-24-10/h1-7,20-21H |
| InChIKey | LZWUNZRMANFRAO-UHFFFAOYSA-N |
| SMILES | C1=CSC(=C1)S(=O)(=O)NC2=CC=C(C=C2)C(C(F)(F)F)(C(F)(F)F)O |
| Reference | 1:ACS Chem Biol. 2011 Mar 18;6(3):218-22. doi: 10.1021/cb1002762. Epub 2010 Dec 6. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist.Kumar N,Kojetin DJ,Solt LA,Kumar KG,Nuhant P,Duckett DR,Cameron MD,Butler AA,Roush WR,Griffin PR,Burris TP, PMID: 21090593 PMCID: PMC3076127 DOI: 10.1021/cb1002762 </br><span>Abstract:</span> Several nuclear receptors (NRs) are still character-ized as orphan receptors because ligands have not yet been identified for these proteins. The retinoic acid receptor-related receptors (RORs) have no well-defined physiological ligands. Here, we describe the identification of a selective RORα synthetic ligand, SR3335 (ML-176). SR3335 directly binds to RORα, but not other RORs, and functions as a selective partial inverse agonist of RORα in cell-based assays. Furthermore, SR3335 suppresses the expression of endogenous RORα target genes in HepG2 involved in hepatic gluconeogenesis including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Pharmacokinetic studies indicate that SR3335 displays reasonable exposure following an ip injection into mice. We assess the ability of SR3335 to suppress gluconeogenesis in vivo using a diet-induced obesity (DIO) mouse model where the mice where treated with 15 mg/kg b.i.d., ip for 6 days followed by a pyruvate tolerance test. SR3335-treated mice displayed lower plasma glucose levels following the pyruvate challenge consistent with suppression of gluconeogenesis. Thus, we have identified the first selective synthetic RORα inverse agonist, and this compound can be utilized as a chemical tool to probe the function of this receptor both in vitro and in vivo. Additionally, our data suggests that RORα inverse agonists may hold utility for suppression of elevated hepatic glucose production in type 2 diabetics. |
