| Identification | Back Directory | [Name]
SR3335 | [CAS]
293753-05-6 | [Synonyms]
SR3335
ML-176
SR3335;ML176
ML-176;SR-3335
ML-176;SR 3335;SR-3335;ML176;ML 176
SR3335;ML-176;SR 3335;SR-3335;ML176;ML 176
SR 3335 (This product is only available in Japan.)
N-[4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)phenyl]thiophene-2-sulfonamide
N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-thiophenesulfonamide
2-Thiophenesulfonamide, N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-
hiophene-2-sulfonic acid [4-(2,2,2-trifluoro-1-hydroxy-1-trifluoroMethyl-ethyl)-phenyl]-aMide
Thiophene-2-sulfonic acid [4-(2,2,2-trifluoro-1-hydroxy-1-trifluoroMethyl-ethyl)-phenyl]-aMide
SR3335,Thiophene-2-sulfonic acid [4-(2,2,2-trifluoro-1-hydroxy-1-trifluoroMethyl-ethyl)-phenyl]-aMide | [Molecular Formula]
C13H9F6NO3S2 | [MDL Number]
MFCD02724814 | [MOL File]
293753-05-6.mol | [Molecular Weight]
405.336 |
| Chemical Properties | Back Directory | [storage temp. ]
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | [solubility ]
insoluble in H2O; ≥87.4 mg/mL in EtOH; ≥88.8 mg/mL in DMSO | [form ]
solid | [color ]
White to off-white | [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(S(NC2=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C=C2)(=O)=O)SC=CC=1 |
| Hazard Information | Back Directory | [Description]
The retinoic acid receptor-related receptors (RORs) are orphan nuclear receptors with diverse putative roles.1,2,3 SR 3335 is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (Ki = 220 nM) and inhibiting constitutive transactivation activity (IC50 = 480 nM).4 It is without effect on RORβ, RORγ, farnesoid X receptor, or liver X receptor α. SR 3335 evokes RORα-dependent effects both in vitro and in vivo, altering gene expression as well as gluconeogenesis.4 | [Uses]
SR3335 (ML 176) is a selective RORα inverse agonist that directly binds to RORα with a Ki of 220 nM[1][2]. | [Definition]
ChEBI: N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-thiophenesulfonamide is a sulfonamide. | [Synthesis]
Under argon protection, 4-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)aniline (A) (1.5 M THF solution, 128 μL, 0.193 mmol) was dissolved in acetone (643 μL). Subsequently, 2,6-dimethylpyridine (29 μL, 0.251 mmol) and 2-thiophenesulfonyl chloride (0.193 mmol) were added sequentially and the reaction was carried out at room temperature. The reaction mixture was heated to 80 °C for 1 day. After completion of the reaction, it was cooled to room temperature and diluted with ethyl acetate (EtOAc) and saturated sodium bicarbonate (NaHCO3) solution. The aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated. The crude product was purified by silica gel column chromatography using hexane/ethyl acetate (7/3) as eluent to afford the target product N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-thiophene-sulfonamide (SR3335) as a white powder in 48 mg (62% yield). The compound has a CAS number of 2937-53-05-6 and is known in the literature and commercially available. | [in vivo]
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].
SR3335 (15 mg/kg/day; ip for 7 days) reduces rhinovirus (RV)-induced lung ILC2s in immature mice (RV infection of 6-day-old BALB/c mice)[3]. | [target]
RORα | [storage]
Store at -20°C | [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. DOI:10.1021/cb1002762
[2] Rajput C, et al. RORα-dependent type 2 innate lymphoid cells are required and sufficient for mucous metaplasia in immature mice. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L983-L993. DOI:10.1152/ajplung.00368.2016 |
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