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SR3335

Catalog No. T5160 CAS 293753-05-6

Synonyms: ML 176

SR3335 (ML 176) is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM).

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SR3335, CAS 293753-05-6

Pack Size	Availability	Price/USD
1 mg	In stock	$ 31.00
5 mg	In stock	$ 72.00
10 mg	In stock	$ 128.00
25 mg	In stock	$ 258.00
50 mg	In stock	$ 478.00
100 mg	In stock	$ 689.00
1 mL * 10 mM (in DMSO)	In stock	$ 79.00

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Purity: 99.41%

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Description	SR3335 (ML 176) is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM).
Targets&IC50	RORα:220 nM(ki)
In vitro	KHS101 increased neuronal differentiation of adherently cultured rat NPCs in a dose-dependent fashion (EC50 ～ 1 μM). KHS101-induced neuron formation (40–60% TuJ1+ cells at 1.5–5 μM KHS101) was also observed under neurosphere-forming conditions in secondary neurospheres derived from both the hippocampus and the subventricular zone (SVZ) of adult rats [1]. In HCC cell lines, KHS101 suppressed cell growth and sphere formation as well as the expression of stem cell transcription factors, including Bmi1, c-Myc, and Nanog. Silencing TACC3 may suppress the Wnt/β-catenin and PI3K/AKT signaling pathways, which regulate cancer stem cell-like characteristics [2]. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101 promoted aggregation of proteins regulating mitochondrial integrity and energy metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were selectively impaired in KHS101-treated GBM cells [3].
In vivo	In two intracranial patient-derived xenograft tumor models in mice, systemic administration of KHS101 reduced tumor growth and increased survival without discernible side effects. The doses of 6 mg/kg KHS101 (i.v. and s.c.) resulted in reasonable plasma concentrations (>1.5 μM) with a plasma half-life of 1.1–1.4 h, and relative bioavailability of 69% following s.c. dosing. Most importantly, the distribution of KHS101 to the brain was extensive as demonstrated by a brain-to-plasma AUC(0–3h) ratio of ～8 (dosing: 3 mg/kg KHS101, i.v.) [3].
Cell Research	Rat NPCs were derived and cultured as described previously by others. After hippocampal cell isolation, the number of dissociated cells was determined and ～5 × 10^5 cells were plated in 60-mm uncoated plates. After overnight incubation (37 °C, 5% CO2, and 95% humidity), the medium was changed and the cells were expanded and maintained in an undifferentiated state on polyornithine- (10 μg/mL in water) and laminin-coated (5 μg/mL in PBS;) dishes in DMEM/F12 supplemented with N2 and basic fibroblast growth factor (bFGF, 20 ng/mL;). For KHS101 and shRNA-induction experiments, early passage cells (passaged no more than six times after hippocampal isolation) were trypsinized and plated at a density of ～1,000 cells/cm2 into N2 medium (DMEM/F12 supplemented with N2) containing KHS analogs (e.g., KHS101, KHS92, and NP; SI Text) at different concentrations (0.5–5 μM) or DMSO (0.1%), RA (1–2 μM), BDNF (100 ng/mL), and/or BMP4 (50–100 ng/mL) for 4 d [1].
Animal Research	To investigate the pharmacokinetic properties of KHS101, male Sprague–Dawley rats were administered 3 mg/kg KHS101 i.v. or s.c. One rat was killed per time point at 5 min, 40 min, 1 h, and 3 h after dosing, and samples of blood (100 μL) and whole brains were collected. In a separate study, rats were administered 6 mg/kg KHS101 i.v. or s.c. Five blood samples of 100 μL each were collected serially via a jugular vein catheter at 2 min (i.v. only), 0.5 h (s.c. only), and 1, 3, 7 and 24 h after dosing. Plasma and homogenized whole brain samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). To study neuronal differentiation upon KHS101 administration in vivo, adult Fisher 344 rats (～10 wk old) received s.c. injections of 6 mg/kg KHS101 or vehicle control (5% ethanol in 15% Captisol). All rats received one daily i.p. injection of 200 mg/kg BrdU for 6 consecutive days after the first day. After 14 d, the animals were killed and perfusion fixed, and the brains were removed and subjected to immunohistochemical analysis [1].

Synonyms	ML 176
Molecular Weight	405.34
Formula	C13H9F6NO3S2
CAS No.	293753-05-6

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 30 mg/mL

DMSO: 50 mg/mL (123.35 mM)

References and Literature

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. 2. Sadeghi H, et al. The retinoid-related orphan receptor alpha is essential for the end-stage effector phase of experimental epidermolysis bullosa acquisita. J Pathol. 2015 Sep;237(1):111-22.

Related compound libraries

This product is contained In the following compound libraries：

Lipid Metabolism Compound Library Metabolism Compound Library Target-Focused Phenotypic Screening Library Bioactive Compound Library Anti-Metabolism Disease Compound Library Bioactive Compounds Library Max Nuclear Receptor Compound Library NO PAINS Compound Library Kinase Inhibitor Library

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XY101 TAK-828F TMP780 RORγt Inverse agonist 8 SR1001 Nobiletin Methyl-3β-hydroxycholenate 3-Oxo-5β-cholanoic acid

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Keywords

SR3335 293753-05-6 Metabolism ROR RAR-related orphan receptor ML 176 inhibit Inhibitor SR-3335 ML-176 SR 3335 ML176 inhibitor

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