sch 58261  (Tocris)

Journal: Bioactive Materials

Article Title: Immunomodulatory supramolecular hydrogel for rheumatoid arthritis management via adenosine A2A receptor-mediated macrophage remodeling

doi: 10.1016/j.bioactmat.2025.11.031

Figure Lengend Snippet: The design of an inflammatory macrophages-targeted, acid-sensitive PNSH for delivery MTX and its role in promoting A2AR activation on M2 macrophages for arthritis therapy. (A)The structure of acid-sensitive polymer-nanomedicine supramolecular hydrogels, composed of drug-loaded MTX NPs. (B) Schematic illustration of arthritis therapy targeting inflammatory joint network via mPECN NPs-mediated release of MTX. This approach leverages MTX targeting the A2AR and repolarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Activation of A2AR and macrophage repolarization by mPECN-MTX NPs synergistically enhanced the anti-inflammatory effect of PNSH-mediated nanomedicine in an arthritis rat model.

Article Snippet: The selective adenosine A2A receptor (A2AR) antagonist SCH58261 (HY-19533) was purchased from MedChemExpress (Shanghai, China).

Techniques: Activation Assay, Polymer

Journal: Bioactive Materials

Article Title: Immunomodulatory supramolecular hydrogel for rheumatoid arthritis management via adenosine A2A receptor-mediated macrophage remodeling

doi: 10.1016/j.bioactmat.2025.11.031

Figure Lengend Snippet: MTX@PNSH promotes anti-inflammatory M2 macrophages through the A2AR signaling pathway. (A) The intracellular cAMP levels in Raw 264.7 cells were determined by homogeneous time-resolved fluorescence (HTRF) following different treatments. (B) qRT-PCR analysis of relative mRNA of A2ar with different treatments. (C) Immunostaining of A2AR expression in Raw 264.7 cells with different treatments. (D) Flow cytometry analysis of A2AR + cells in Raw 264.7 cells with different treatments and the percentage of A2AR + cells in Raw 264.7 cells with different treatments. (E) qRT-PCR analysis of relative mRNA expression of Pdl1 without LPS treatment. (F) qRT-PCR analysis of relative mRNA expression of Ido1 without LPS treatment. (G) qRT-PCR analysis of relative mRNA expression of Pdl1 with LPS treatment. (H) qRT-PCR analysis of relative mRNA expression of Ido1 with LPS treatments. (I) Western blotting analysis of A2AR protein level in macrophages after 24 h of different treatment with or without A2AR inhibitor. (J) Quantitative analysis of A2AR protein level in different treatments with or without A2AR inhibitor. (K) Flow cytometry analysis of CD11b and CD39 in Raw 264.7 cells with different treatments and the percentage of CD11b + CD39 + macrophages. (L) Flow cytometry analysis of CD11b and CD73 in Raw 264.7 cells with different treatments and the percentage of CD11b + CD73 + macrophages. (M) Flow cytometry analysis of CD11b and PD-L1 in Raw 264.7 cells after 24 h of different treatments and the percentage of CD11b + PD-L1 + macrophages in Raw 264.7 cells after 24 h of different treatments. Data are presented as mean ± SD, n = 3. Statistical significance was determined using one-way ANOVA, followed by Dunnett's post hoc test for comparisons between groups.

Article Snippet: The selective adenosine A2A receptor (A2AR) antagonist SCH58261 (HY-19533) was purchased from MedChemExpress (Shanghai, China).

Techniques: Fluorescence, Quantitative RT-PCR, Immunostaining, Expressing, Flow Cytometry, Western Blot

Journal: Drug Design, Development and Therapy

Article Title: Cordycepin Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Inhibiting IL-6/IL-6R-Mediated p38 MAPK and NF-κB Activation Through Adenosine A 2A Receptor Stimulation

doi: 10.2147/DDDT.S575035

Figure Lengend Snippet: Cordycepin abates DSS-induced damage in NCM460 cells by activating adenosine receptor A 2A . ( A ) The cAMP levels in NCM460 cells under treatment with 2% DSS and/or 1 μmol/L and 10 μmol/L COR. ( B ) The cAMP levels in NCM460 cells under treatment with 2% DSS, 10 μmol/L COR, 5 μmol/L SCH58261 (SCH), and / or 5 μmol/L DPCPX for 24 h. The release levels of ( C ) LDH, ( D ) IL-1β, ( E ) IL-6, and ( F ) TNF-α were measured by using Elisa. ( G ) Representative images of PI staining and the percentage of PI-positive cells, scar bar = 100 μm. ( H – J ) The protein expression of ZO-1, A 2A AR and A 1 AR in NCM460 cells was determined by using Western blotting assay. The results were representative of three independent experiments and expressed as mean ± SEM. Data were compared using two-tailed Student’s t tests. vs. control group; # P < 0.05, vs. control group; *P < 0.05, **P < 0.01 and ***P < 0.001 vs. the 2% DSS group.

Article Snippet: Cordycepin (COR, CAS No. 73–03-0, Cat. No. C805132, 98% purity) was purchased from Shanghai Macklin Biochemical Technology Co., Ltd. (China); Dextran Sodium Sulfate (DSS, 60316ES60) was provided by Yeasen Biotechnology Co., Ltd. (Shanghai, China); Sulfasalazine (SASP, S129986) was obtained from Shanghai Aladdin Biochemical Technology Co., Ltd. (China); SCH58261 (HY-19533) and DPCPX (HY-100937) were supplied by MedChemExpress (MCE, Monmouth Junction, NJ, USA); BisBenzimide H 33342 (Hoechst 33342, C0030), and Propidium Iodide (PI, C0080) were purchased from Beijing Solarbio Science & Technology Co., Ltd. Proteintech Co., Ltd. (Wuhan, China), supplied the antibody against Zonula Occludens-1 (ZO-1, 21,773-1-AP), Occludin Polyclonal antibody (27260-1-AP), Adenosine A 1 receptor Polyclonal antibody (A 1 AR, 20332-1-AP), the antibody against β-actin (20536-1-AP), CD126/IL-6R alpha Polyclonal antibody (23457-1-AP), Horseradish peroxidase (HRP)-conjugated goat anti-rabbit secondary antibody (SA00001-2), and HRP-conjugated goat anti-mouse secondary antibody (SA00001-1).

Techniques: Enzyme-linked Immunosorbent Assay, Staining, Expressing, Western Blot, Two Tailed Test, Control

Journal: Drug Design, Development and Therapy

Article Title: Cordycepin Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Inhibiting IL-6/IL-6R-Mediated p38 MAPK and NF-κB Activation Through Adenosine A 2A Receptor Stimulation

doi: 10.2147/DDDT.S575035

Figure Lengend Snippet: SCH58261 blocks cordycepin’s ameliorative effects on DSS-induced acute colitis symptoms in mice. ( A ) Animal experimental flowchart. ( B ) The body weight change. ( C ) The disease activity index (DAI). ( D ) The colon length. ( E – I ) Serum level of TNF-α, IL-1β, IL-6, IFN-γ and CRP. ( J ) The histopathological damage of colons was detected by using H&E staining. ( K ) Histological score. Data were presented as the means ± SEM of six-eight mice in each group and were compared using two-tailed Student’s t tests. ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs. control group; *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 vs. the DSS model (DSS) group.

Article Snippet: Cordycepin (COR, CAS No. 73–03-0, Cat. No. C805132, 98% purity) was purchased from Shanghai Macklin Biochemical Technology Co., Ltd. (China); Dextran Sodium Sulfate (DSS, 60316ES60) was provided by Yeasen Biotechnology Co., Ltd. (Shanghai, China); Sulfasalazine (SASP, S129986) was obtained from Shanghai Aladdin Biochemical Technology Co., Ltd. (China); SCH58261 (HY-19533) and DPCPX (HY-100937) were supplied by MedChemExpress (MCE, Monmouth Junction, NJ, USA); BisBenzimide H 33342 (Hoechst 33342, C0030), and Propidium Iodide (PI, C0080) were purchased from Beijing Solarbio Science & Technology Co., Ltd. Proteintech Co., Ltd. (Wuhan, China), supplied the antibody against Zonula Occludens-1 (ZO-1, 21,773-1-AP), Occludin Polyclonal antibody (27260-1-AP), Adenosine A 1 receptor Polyclonal antibody (A 1 AR, 20332-1-AP), the antibody against β-actin (20536-1-AP), CD126/IL-6R alpha Polyclonal antibody (23457-1-AP), Horseradish peroxidase (HRP)-conjugated goat anti-rabbit secondary antibody (SA00001-2), and HRP-conjugated goat anti-mouse secondary antibody (SA00001-1).

Techniques: Activity Assay, Staining, Two Tailed Test, Control

Journal: Drug Design, Development and Therapy

Article Title: Cordycepin Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Inhibiting IL-6/IL-6R-Mediated p38 MAPK and NF-κB Activation Through Adenosine A 2A Receptor Stimulation

doi: 10.2147/DDDT.S575035

Figure Lengend Snippet: SCH58261 blocks cordycepin’s amelioration of intestinal inflammation and gut barrier function in DSS-induced colitis mice. ( A – C ) Level of colonic IL-1β, IL-6, and TNF-α among the Control, DSS, DSS+COR-L and DSS+COR-H group were detected by using Elisa. ( D ) Representative images of AB-PAS staining of colonic tissue. The arrow indicates the goblet cells. ( E ) Number of goblet cells in colonic tissue. ( F ) Representative images of TUNEL staining in colonic tissue, scale bar = 50 μm. ( G ) Percentage of TUNEL-positive cells (%). ( H ) The protein expression of ZO-1 and Occludin in colons was determined by using Western blotting assay. ( I ) and ( J ) Serum level of D-lactate and diamine oxidase (DAO) were measured by using Elisa. ( K ) The serum cAMP levels among the control, DSS, DSS+COR-L, DSS+COR-H group and DSS+SCH+COR-H group. Data were presented as the means ± SEM of six-eight mice in each group and were compared using two-tailed Student’s t tests. # P < 0.05, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs. control group; *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 vs. the DSS model (DSS) group.

Article Snippet: Cordycepin (COR, CAS No. 73–03-0, Cat. No. C805132, 98% purity) was purchased from Shanghai Macklin Biochemical Technology Co., Ltd. (China); Dextran Sodium Sulfate (DSS, 60316ES60) was provided by Yeasen Biotechnology Co., Ltd. (Shanghai, China); Sulfasalazine (SASP, S129986) was obtained from Shanghai Aladdin Biochemical Technology Co., Ltd. (China); SCH58261 (HY-19533) and DPCPX (HY-100937) were supplied by MedChemExpress (MCE, Monmouth Junction, NJ, USA); BisBenzimide H 33342 (Hoechst 33342, C0030), and Propidium Iodide (PI, C0080) were purchased from Beijing Solarbio Science & Technology Co., Ltd. Proteintech Co., Ltd. (Wuhan, China), supplied the antibody against Zonula Occludens-1 (ZO-1, 21,773-1-AP), Occludin Polyclonal antibody (27260-1-AP), Adenosine A 1 receptor Polyclonal antibody (A 1 AR, 20332-1-AP), the antibody against β-actin (20536-1-AP), CD126/IL-6R alpha Polyclonal antibody (23457-1-AP), Horseradish peroxidase (HRP)-conjugated goat anti-rabbit secondary antibody (SA00001-2), and HRP-conjugated goat anti-mouse secondary antibody (SA00001-1).

Techniques: Control, Enzyme-linked Immunosorbent Assay, Staining, TUNEL Assay, Expressing, Western Blot, Two Tailed Test

Journal: Frontiers in Pharmacology

Article Title: Adenosine A 2A receptors regulate D 2 -type medium spiny neurons in the nucleus accumbens to mediate pain and depression comorbidity

doi: 10.3389/fphar.2026.1759544

Figure Lengend Snippet: A 2A Rs modulated the excitability of D 2 -MSNs in the NAcS (A) Timeline of the stereotactic injection and ex vivo electrophysiology (B) Typical micrograph showing the electrophysiological recording of mCherry-labeled NAcS D 2 -MSNs, scale bar = 10 µm (C) Sample of whole-cell recording of action potentials in the NAcS after 0.1 µM CGS 21680 perfusion (D) (left) 0.1 µM CGS 21680 perfusion increased the number of eAPs of mCherry-labeled neurons (right) The minimal voltage threshold to induce eAPs was lower after perfusion with 0.1 µM CGS 21680 (n = 9 cells from 4 mice) (E) Sample of whole-cell recording of action potentials in the NAcS after 0.1 µM SCH 58261 perfusion (F) (left) 0.1 µM SCH 58261 perfusion decreased the number of eAPs of mCherry-labeled neurons (right) The minimal voltage threshold to induce eAPs was higher after perfusion with 0.1 µM SCH 58261 (n = 12 cells from 4 mice) Data are shown as mean ± s.e.m. , ** P < 0.01, *** P < 0.001.

Article Snippet: The A 2A R agonist CGS 21680 (MedChemExpress, HY-13201A) and antagonist SCH 58261 (MedChemExpress, HY-19533) were initially dissolved in 100% dimethyl sulfoxide (DMSO) to prepare 10 mM stock solutions and stored at −20 °C.

Techniques: Injection, Ex Vivo, Labeling

Journal: Frontiers in Pharmacology

Article Title: Adenosine A 2A receptors regulate D 2 -type medium spiny neurons in the nucleus accumbens to mediate pain and depression comorbidity

doi: 10.3389/fphar.2026.1759544

Figure Lengend Snippet: NAcS A 2A Rs antagonism alleviated SNI-induced pain-depression comorbidity (A) Timeline of cannula and SNI surgery, intracerebral injection, Von Frey and Hargreaves tests at specified time points (B,C) 50%PWTs (B) and PWL (C) in mice treated with vehicle or SCH 58261 (4 ng/side) 1 W following SNI surgery (n = 8 mice/group) (D–F) 50% PWTs (D) , PWL (E) , and immobile time in the FST (F) after a single microinjection of vehicle or SCH 58261 (4 ng/side) 6 W following SNI surgery (n = 8 mice/group) (G–I) 50% PWTs (G) , PWL (H) , and immobile time in the FST (I) after five consecutive microinjections of vehicle or SCH 58261 (4 ng/side) 6 W following SNI surgery (n = 8 mice/group). Data are represented as mean ± s.e.m. , * P < 0.05, ** P < 0.01, *** P < 0.001, ns means no significance.

Article Snippet: The A 2A R agonist CGS 21680 (MedChemExpress, HY-13201A) and antagonist SCH 58261 (MedChemExpress, HY-19533) were initially dissolved in 100% dimethyl sulfoxide (DMSO) to prepare 10 mM stock solutions and stored at −20 °C.

Techniques: Injection, Microinjection