sr2211  (MedChemExpress)

Journal: Frontiers in Immunology

Article Title: Altered Th17/Treg balance and therapeutic targeting of RORγ in primary focal hyperhidrosis

doi: 10.3389/fimmu.2025.1656632

Figure Lengend Snippet: SR2211, the inverse agonist of RORγ, attenuated the sweat secretion and Th17 lymphocyte related inflammatory response in hyperhidrosis mice. Mice were administered with vehicle or SR2211 for one week before the induction of hyperhidrosis, as shown in (A) . The number of black dots were calculated (B) . The number of sweat secretory granules were counted (C) and the concentration of acetylcholine in serum was detected by ELISA (D) . Th17 lymphocyte subpopulations in peripheral blood of the mice were compared (E) . The serum levels of IL-17 (F) and IL-6 (G) were measured by ELISA. Western blotting was used to detect the protein expression of IL-17A in the sweat gland of hyperhidrosis mice (H) . GAPDH was used as a loading control and the expressions were normalized to control (I) . The data were presented with mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 from Brown-Forsythe ANOVA test followed by Dunnett’s T3 multiple comparisons test.

Article Snippet: SR2211 was purchased from MedChemExpress (MCE, Cat# HY-16998).

Techniques: Concentration Assay, Enzyme-linked Immunosorbent Assay, Western Blot, Expressing, Control

Journal: bioRxiv

Article Title: RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression

doi: 10.1101/2023.11.19.567414

Figure Lengend Snippet: a, Experimental design: adult wt C3H/HeJ mice were fed with HCD for 8 weeks before being injected with K1735-M2 tumor cells. When the tumor volume reached ∼0.80-1.00 cm 3 , typically 20-24 days after tumor cell injection, primary tumors were surgically removed. Twenty-eight days after tumor removal, mice were sacrificed for sample collection and analysis. SR2211 was administered to a first group of mice 10 days before tumor removal (SR2211_PRE). A second group of mice received SR2211 treatment 5 days after tumor removal (SR2211_POST). b, Lung metastatic areas (n=5) in HCD-fed K1735-M2 mice treated with either SR2211 or vehicle control. Representative images are shown. Scale bar, 1mm. c, Lung metastatic areas in NCD- or HCD-fed MN/MCA1 wt mice treated with vehicle, SR2211, anti-PD1, or SR2211 plus anti-PD1 (n=5). Representative images are shown. Scale bar, 1mm. One experiment was performed. Data are expressed as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. One-way ANOVA with Tukey’s multiple comparisons test.

Article Snippet: Starting from day 10 after tumor cell injection, MN/MCA1-bearing mice received intraperitoneal treatment with the following reagents: anti-IL6 monoclonal antibody (BioXcell, Clone MP5-20F3) at a dose of 200 μg twice a week; anti-IL1 (anakinra, Sobi, Stockholm, Sweden) at a dose of 200 μg twice a week; anti-PCSK9 monoclonal antibody mAb1 (kindly provided by Amgen Inc, Thousand Oaks, CA, USA) at a dose of 200 μg per mouse twice a week (MN/MCA1 tumor) or once a week (KP mice); anti-CSF1R monoclonal antibody (BioXcell, Clone AFS98) at an initial dose of 400 μg per mouse, followed by twice-weekly doses of 200 μg for the duration of the experiment; anti-CCR2 inhibitor (Tocris) at a dose of 75 μg per mouse twice a week; and the RORγ inverse agonist SR2211 (Tocris) at a dose of 50 μg per mouse twice a week.

Techniques: Injection, Control

Journal: bioRxiv

Article Title: RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression

doi: 10.1101/2023.11.19.567414

Figure Lengend Snippet: MN/MCA1 mice were fed NCD or HCD. a-d, Frequency of RORγ + CCR2 + cells and relative RORγ expression levels in: a, M-MDSCs from tumors (n=6); b, lung IMs (n=4), AMs (n=4), and M- MDSCs (n=5); c, BM M-MDSCs (n=5); d, Spleen M-MDSCs (n=5). e, Frequency of RORγ + CCR2 - cells and relative RORγ expression levels in lung AMs (n=4), BM or spleen M-MDSCs (n=5). f, Frequency of RORγ + CMPs and GMPs cells and relative RORγ expression levels (n=4). g, HEK293 cells were co-transfected with CMV-RORγ and IL17A_prom-Luc plasmids. Plasmid 1: RORγ gene is constitutively expressed under the control of CMV promoter. Plasmid 2: Luciferase reporter gene is under the control of the minimal promoter of Il17a gene, whose transcription is driven by RORγ. h-j, HEK293 cells, co-transfected with plasmids 1 and 2, were stimulated with SR0987, desmosterol, cholesterol, or LDL ( h ), or with sera from NCD- or HCD-fed MN/MCA1 TB or TF mice (n=4) ( i ), or exposed to single or combinations of cholesterol, SR2211 and TCM ( j ). Luciferase activity was quantified as relative light units (RLU). Data are representative of five ( a, b, d ), two ( c, e, h-j ), or three ( f ) independent experiments. Data are expressed as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between selected relevant comparisons. a-f, Unpaired two-tailed t -test; h-j, One-way ANOVA with Tukey’s multiple comparisons test.

Article Snippet: Starting from day 10 after tumor cell injection, MN/MCA1-bearing mice received intraperitoneal treatment with the following reagents: anti-IL6 monoclonal antibody (BioXcell, Clone MP5-20F3) at a dose of 200 μg twice a week; anti-IL1 (anakinra, Sobi, Stockholm, Sweden) at a dose of 200 μg twice a week; anti-PCSK9 monoclonal antibody mAb1 (kindly provided by Amgen Inc, Thousand Oaks, CA, USA) at a dose of 200 μg per mouse twice a week (MN/MCA1 tumor) or once a week (KP mice); anti-CSF1R monoclonal antibody (BioXcell, Clone AFS98) at an initial dose of 400 μg per mouse, followed by twice-weekly doses of 200 μg for the duration of the experiment; anti-CCR2 inhibitor (Tocris) at a dose of 75 μg per mouse twice a week; and the RORγ inverse agonist SR2211 (Tocris) at a dose of 50 μg per mouse twice a week.

Techniques: Expressing, Transfection, Plasmid Preparation, Control, Luciferase, Activity Assay, Two Tailed Test

Journal: bioRxiv

Article Title: RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression

doi: 10.1101/2023.11.19.567414

Figure Lengend Snippet: a-h , NCD- or HCD-fed MN/MCA1 wt mice treated with the RORγ inhibitor SR2211 or vehicle control (n=4). a, Lung metastatic area; representative images are shown, scale bar, 1 mm; b, tumor growth (volume and weight); c, total blood cholesterol; d, FACS quantification of TAMs and relative CCR2 expression; e , TNFα, MHC-II, and CD206 expression by TAMs (MFI); f, frequency of IM (top) and AM (bottom) subsets and relative expression (MFI) of CCR2, MHC-II, and CD206; g, CMP and GMP frequencies in BM; h , IFNγ, PD-1 and CTLA4 expression (MFI) in intratumoral CD8 + T cells. i-l, HCD-fed K1735-M2-bearing wt mice treated with SR2211 or vehicle control. i, Tumor weight (n=6); j, FACS quantification of TAMs and tumor-infiltrating M-MDSCs (n=4); k, IM and AM frequencies and relative TNFα expression (MFI) (n=5); l, IFNγ, PD1, and CTLA4 expression (MFI) by lung CD8 + T cells (n=5). m, Tumor growth (volume and weight) in NCD- or HCD-fed wt mice treated with vehicle, SR2211, anti-PD1, or SR2211 plus anti-PD1 (n=5). One experiment was performed. Data are expressed as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between selected relevant comparisons. a, b (right) , c-h, k, l, m (right), One-way ANOVA with Tukey’s multiple comparisons test. i, j, Unpaired two-tailed t -test. b (left) , m (left), Two-way ANOVA with Tukey’s multiple comparisons test

Article Snippet: Starting from day 10 after tumor cell injection, MN/MCA1-bearing mice received intraperitoneal treatment with the following reagents: anti-IL6 monoclonal antibody (BioXcell, Clone MP5-20F3) at a dose of 200 μg twice a week; anti-IL1 (anakinra, Sobi, Stockholm, Sweden) at a dose of 200 μg twice a week; anti-PCSK9 monoclonal antibody mAb1 (kindly provided by Amgen Inc, Thousand Oaks, CA, USA) at a dose of 200 μg per mouse twice a week (MN/MCA1 tumor) or once a week (KP mice); anti-CSF1R monoclonal antibody (BioXcell, Clone AFS98) at an initial dose of 400 μg per mouse, followed by twice-weekly doses of 200 μg for the duration of the experiment; anti-CCR2 inhibitor (Tocris) at a dose of 75 μg per mouse twice a week; and the RORγ inverse agonist SR2211 (Tocris) at a dose of 50 μg per mouse twice a week.

Techniques: Control, Expressing, Two Tailed Test

Journal: Frontiers in Immunology

Article Title: Altered Th17/Treg balance and therapeutic targeting of RORγ in primary focal hyperhidrosis

doi: 10.3389/fimmu.2025.1656632

Figure Lengend Snippet: SR2211, the inverse agonist of RORγ, attenuated the sweat secretion and Th17 lymphocyte related inflammatory response in hyperhidrosis mice. Mice were administered with vehicle or SR2211 for one week before the induction of hyperhidrosis, as shown in (A) . The number of black dots were calculated (B) . The number of sweat secretory granules were counted (C) and the concentration of acetylcholine in serum was detected by ELISA (D) . Th17 lymphocyte subpopulations in peripheral blood of the mice were compared (E) . The serum levels of IL-17 (F) and IL-6 (G) were measured by ELISA. Western blotting was used to detect the protein expression of IL-17A in the sweat gland of hyperhidrosis mice (H) . GAPDH was used as a loading control and the expressions were normalized to control (I) . The data were presented with mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 from Brown-Forsythe ANOVA test followed by Dunnett’s T3 multiple comparisons test.

Article Snippet: To validate the clinical relevance of these findings and evaluate the therapeutic potential of immunomodulation, we established a pilocarpine-induced mouse model of hyperhidrosis and assessed the effects of SR2211, a selective RORγ antagonist (MedChemExpress, Cat# HY-16998, purity 99.67%) with low reported off-target activity against RORα, RORβ, and kinases such as TRK and BRAF.

Techniques: Concentration Assay, Enzyme-linked Immunosorbent Assay, Western Blot, Expressing, Control

Journal: Nature Communications

Article Title: Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation

doi: 10.1038/s41467-022-32089-3

Figure Lengend Snippet: Analysis of cytokine ( n = 9) and transcription factor ( n = 12) expression in differentiated human ILCP after addition of either 0.01% DMSO or SR2211 (10 uM) was assessed as described in Fig. . Representative plots in Supplementary Fig. . Expression of Group 1 ILC associated factors ( a ) IFN γ and b T-BET. Expression of Group 2 ILC associated factors ( c ) IL-13 ( d ) and GATA-3. Expression of Group 3 ILC associated factors ( e ) IL-17A and f IL-22 ( g ) RORγt. Data compared using paired T-tests (two-tailed), details in Supplementary Table . ns = not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p < 0.001. Data are presented as individual unique donors matched across conditions. Results from 3 ( a , c , e , f ) or 4 ( b , d , g ) independent experiments. Source Data are provided as a Source Data file.

Article Snippet: The specific RORC inhibitor SR2211 was purchased commercially (Tocris/Biotechne) and resuspended in DMSO at a stock of 100 mM.

Techniques: Expressing, Two Tailed Test

Journal: Nature Communications

Article Title: Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation

doi: 10.1038/s41467-022-32089-3

Figure Lengend Snippet: Single ILCP from healthy donors ( n = 16) were cultured with either 0.01% DMSO (black circles) or SR2211 (10 μ M) (red). a Frequencies of unipotent (EOMES + ILC1, EOMES-ILC1, ILC2, ILC3, None) and total multipotent clones per individual healthy donor. b Frequencies of types of multipotent clones. c Overall distributions of clones grown in either DMSO alone or SR2211. d Overall frequencies of all clones expressing IFNγ, IL-13, IL-17A and IL-22. e Cloning efficiency of donors grown in either DMSO or SR2211. Comparisons performed using ( a – b , d ) Two-way ANOVA with matching using Šidák’s multiple comparisons tests, (details in Supplementary Table ) ( c ) chi-square test (observed vs expected; details in Supplementary Table ) and e paired t-test (two-tailed) (details in Supplementary Table ). ns = not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p < 0.001. Data represented as individual donors matched across conditions, compiled from 7 experiments. Source Data are provided as a Source Data file.

Article Snippet: The specific RORC inhibitor SR2211 was purchased commercially (Tocris/Biotechne) and resuspended in DMSO at a stock of 100 mM.

Techniques: Cell Culture, Clone Assay, Expressing, Two Tailed Test

Journal: Cancers

Article Title: Deregulation of Cholesterol Homeostasis by a Nuclear Hormone Receptor Crosstalk in Advanced Prostate Cancer

doi: 10.3390/cancers14133110

Figure Lengend Snippet: RORγ antagonists inhibit mCRPC cell growth and survival by decreasing intracellular cholesterol levels. ( a , b ) Cell viability, measured by Cell-Titer GLO (Promega) of 22Rv1 ( a ) and C4-2B ( b ) cells treated with the indicated concentration of RORγ antagonists XY018 and SR2211 for 4 d. ( c ) Total cholesterol levels in relative florescent units/protein, measured by Amplex TM Red Cholesterol Assay Kit of 22Rv1 cells treated with indicated concentration of XY018 for 72 h. ( d , e ) Cell numbers of 22Rv1 ( d ) and C4-2B ( e ) cells treated with indicated concentration of XY018, SR2211, and cholesterol for 48 h. Data are shown as mean ± s.d. n = 3. Student’s t test. * p < 0.05, ** p < 0.01.

Article Snippet: SR2211 (Purity > 98%) was obtained from TOCRIS (Bristol, UK).

Techniques: Concentration Assay, Cholesterol Assay

Journal: bioRxiv

Article Title: RORA regulates neutrophil migration and activation in zebrafish

doi: 10.1101/2021.12.03.470833

Figure Lengend Snippet: (A, B) Tracks and quantification of neutrophil motility in zebrafish larva treated with SR3335 (100μM), SR2211 (100μM), or VPR66 (25μM). Scale bar, 200 µm. Three embryos, each from three different founders, were imaged. Quantification of neutrophils in one representative video is shown, Kruskal–Wallis test. (C, D) Representative images and quantification of neutrophils recruited to the infected ear in zebrafish larva treated with RORα specific inhibitor (SR3335, 100μM), RORγ specific inhibitor (SR2211, 100μM) or pan-ROR family inhibitor (VPR66, 25μM). Scale bar, 100 µm. (E, F) Representative images and quantification of neutrophils recruited to tail fin transection sites in zebrafish larva treated with SR3335 (100μM), SR2211 (100μM), or VPR66 (25μM). Scale bar: 500 µm. (C-F) The result from one representative experiment is shown as mean, Mann–Whitney test. (G, H) Representative tracks and mean velocity of primary human neutrophils treated with SR3335 (50μM), SR2211 (50μM), or SR1001 (pan-ROR family inhibitor) (50 µM) migrating towards fMLP in 3D matrigel. Scale bar, 100 µm. Representative results for three individual trials are shown. The result is presented as mean, Mann–Whitney test. (I) Neutrophil recruitments after zebrafish tail wounding at different dosages of SR3335 treatment compared to 1% DMSO treatment, Kruskal–Wallis test. (J) Transwell migration of primary human neutrophils treated with DMSO (0.1%) or SR3335 at 10, 30, or 100 μM toward 100 nM fMLP. Results are presented as mean ± s.d., from three independent experiments and normalized to DMSO (0.1%), Kruskal–Wallis test.

Article Snippet: ROR inhibitors SR3335 (Cayman # 12072), SR2211 (Cayman # 11972), SR1001 (Cayman # 10922), and VPR-66 (Novus # NBP2-29335) were dissolved in DMSO to make a 100 mM stock, then further diluted in E3 to working concentrations (10-100 μM for recruitment and motility assays, and indicated concentration for survival assays).

Techniques: Infection, MANN-WHITNEY, Migration

Journal: bioRxiv

Article Title: RORA regulates neutrophil migration and activation in zebrafish

doi: 10.1101/2021.12.03.470833

Figure Lengend Snippet: (A) Survival curve of 3 dpf larvae from the vector or miR-99 line after i.v. infection with Pseudomonas aeruginosa (PAK). (B) Survival curve of 3 dpf larvae from the mcherry or roraa DN line larvae after i.v. infection with PAK. (C) Survival curve of 3 dpf larvae treated with DMSO or SR3335 (100µM) injected with PAK. (D) Survival curve of 3 dpf larvae treated with DMSO or SR2211 (100µM) injected with PAK. One representative experiment of three independent biological repeats (n = 20 each group) is shown. The result is analyzed with Gehan– Breslow–Wilcoxon test.

Article Snippet: ROR inhibitors SR3335 (Cayman # 12072), SR2211 (Cayman # 11972), SR1001 (Cayman # 10922), and VPR-66 (Novus # NBP2-29335) were dissolved in DMSO to make a 100 mM stock, then further diluted in E3 to working concentrations (10-100 μM for recruitment and motility assays, and indicated concentration for survival assays).

Techniques: Plasmid Preparation, Infection, Injection