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Chemical Structure| 1335106-03-0 Chemical Structure| 1335106-03-0

Structure of SR1001
CAS No.: 1335106-03-0

Chemical Structure| 1335106-03-0

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SR1001 is a selective RORα and RORγ inverse agonist and inhibits TH17 cell differentiation and function.

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Product Details of SR1001

CAS No. :1335106-03-0
Formula : C15H13F6N3O4S2
M.W : 477.40
SMILES Code : CC(NC1=NC(C)=C(S(=O)(NC2=CC=C(C(C(F)(F)F)(O)C(F)(F)F)C=C2)=O)S1)=O
MDL No. :MFCD23160036
InChI Key :OZBSSKGBKHOLGA-UHFFFAOYSA-N
Pubchem ID :44241473

Safety of SR1001

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319
Precautionary Statements:P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary mouse keratinocytes (MKCs) 10 µM 20 hours Evaluate the effect of SR1001 on MC903-induced Tslp expression, SR1001 showed moderate suppression of Tslp expression in vitro J Invest Dermatol. 2017 Dec;137(12):2523-2531
Human peripheral blood mononuclear cells (hPBMCs) 5 µM 24 hours To evaluate the effect of SR1001 on IL-17 expression in human PBMCs, results showed that SR1001 inhibited IL-17 expression. Nature. 2011 Apr 28;472(7344):491-4
EL4 cells 10 µM 24 hours To evaluate the effect of SR1001 on IL-17A mRNA expression, results showed that SR1001 suppressed Il17a mRNA expression, and this suppression was dependent on ROR α/ROR γ. Nature. 2011 Apr 28;472(7344):491-4
HepG2 cells 10 µM 24 hours Suppression of ENHO gene expression Mol Metab. 2018 Feb;8:51-64
Pancreatic acinar AR42J cells 15 μg/ml 24 hours To investigate the effect of SR1001 on pancreatic acinar cell apoptosis, results showed that SR1001 significantly reduced cell apoptosis. Heliyon. 2023 Sep 18;9(9):e20118
CD4+ T cells 15 μg/ml 24 hours To investigate the effect of SR1001 on Th17 cell differentiation, results showed that SR1001 significantly downregulated Th17 cell differentiation. Heliyon. 2023 Sep 18;9(9):e20118
Primary mouse keratinocytes (MKCs) 10 µM 4 hours Evaluate the effect of SR1001 on TPA-induced inflammatory cytokine expression, SR1001 did not significantly block TPA-induced cytokine expression J Invest Dermatol. 2017 Dec;137(12):2523-2531
Splenocytes 5 µM 5 days To evaluate the effect of SR1001 on T H17 cell differentiation, results showed that SR1001 inhibited the mRNA expression of Il17a, Il17f, Il21, and Il22. Nature. 2011 Apr 28;472(7344):491-4
Human monocyte-derived macrophages 10 µM 7 days SR1001 treatment reduced the expression of the BMAL1 repressor REV ERBα in M1 macrophages and showed a tendency towards reduced viability of the cells. In M2 macrophages, RORβ levels significantly increased. Front Immunol. 2024 May 28;15:1408772

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice MC903-induced atopic dermatitis-like disease model and TPA-induced acute irritant dermatitis model Topical application 0.6 mg (50 mM) Once daily for 11 days (AD model) or single dose followed by 26-hour observation (acute dermatitis model) Evaluate the anti-inflammatory effects of SR1001, SR1001 significantly reduced skin inflammation induced by MC903 and TPA, decreasing inflammatory cell infiltration and cytokine expression J Invest Dermatol. 2017 Dec;137(12):2523-2531
Male C57BL/6J mice High cholesterol diet model Intraperitoneal injection 100 mg/kg Twice daily for 21 days High cholesterol diet suppressed hepatic Enho expression, SR1001 further suppressed expression Mol Metab. 2018 Feb;8:51-64
Mice Depression-like behavior models Intraperitoneal injection 125 µg Once daily, starting one day before Th17 cell transfer and continued throughout the experiment Inhibition of RORγT to reduce Th17 cell differentiation, thereby decreasing depression-like behavior Biol Psychiatry. 2013 Apr 1;73(7):622-30
Mice Experimental autoimmune encephalomyelitis (EAE) model Intraperitoneal injection (i.p.) 25 mg/kg Twice daily, for the duration of the study To evaluate the effect of SR1001 on the EAE model, results showed that SR1001 delayed the onset and clinical severity of EAE and suppressed the mRNA expression of Il17a, Il21, and Il22 in the spinal cord. Nature. 2011 Apr 28;472(7344):491-4
Wistar rats Chronic restraint stress model Intraperitoneal injection 25 mg/kg Daily for 28 days SR1001 treatment significantly ameliorated CRS-induced depressive-like behavior in the sucrose preference test, forced swim test, and novelty-suppressed feeding test. Additionally, SR1001 reduced the expression levels of IL-6, IL-17, and IL-22 in serum. J Neuroinflammation. 2022 Jul 14;19(1):186
BALB/c mice House dust mite (HDM)-induced allergic airway inflammation model Intraperitoneal injection 25 mg/kg Twice daily, for a total of five times SR1001 significantly reduced the proportion of proinflammatory Mo-AMs in the bronchoalveolar lavage fluid (BALF) of mice and decreased immune cell infiltration and goblet cell hyperplasia in lung tissue. Front Immunol. 2024 May 28;15:1408772
Mice LDL-R−/− mice Intraperitoneal injection 25 mg/kg Twice daily for one month SR1001 treatment significantly reduced plaque formation, decreased plasma low-density lipoprotein (LDL) levels without affecting high-density lipoprotein (HDL). Additionally, SR1001 induced an anti-atherogenic immune profile characterized by a reduction in Th17 cells and an increase in Treg and Th2 cells. Mol Metab. 2016 Jul 25;5(10):997-1005
Mice LDL-R−/− mice Intraperitoneal injection 25 mg/kg Twice daily for one month SR1001 treatment significantly decreased plaque formation, reduced plasma LDL levels without affecting HDL, and modulated cholesterol metabolism by increasing intestinal cholesterol excretion. Additionally, SR1001 induced an anti-atherogenic immune profile characterized by a reduction in Th17 cells and an increase in Treg and Th2 cells. Mol Metab. 2016 Jul 25;5(10):997-1005
C57BL/6 mice CLP-induced sepsis-associated pancreatic injury model Intraperitoneal injection 25 mg/kg Once daily for three days To investigate the protective effect of SR1001 on sepsis-associated pancreatic injury, results showed that SR1001 significantly alleviated pancreatic injury and inhibited the RhoA/ROCK1 pathway. Heliyon. 2023 Sep 18;9(9):e20118
Mice STZ-induced diabetic mouse model Subcutaneous injection 5 μM/100 μL Once per week for 2 months or 8 months SR1001 treatment significantly reduced retinal inflammation, oxidative stress, and capillary degeneration in diabetic mice, and decreased leukocyte adhesion and retinal endothelial cell death. Int J Mol Sci. 2020 May 17;21(10):3547

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.09mL

0.42mL

0.21mL

10.47mL

2.09mL

1.05mL

20.95mL

4.19mL

2.09mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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