adenosine a2a receptor a2ar antagonist sch58261  (MedChemExpress)

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: 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

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: A CT26 CRC cells were stained with PKH26GL (red) and quinacrine (green) fluorescent dyes. Images were acquired using confocal microscopy at time 0 and after 5 min following P2X7 activation with 300 µM BzATP and are extrapolated from a 30-min time course (see supplementary videos and ). B CT26 cells were pre-treated with P2X7 antagonist AZ10606120 (5 µM) for 10 min before application of BzATP. C Number of vesicles released in 30 min from CT26 cells in PBS vehicle (PBS S-VS), following stimulation with P2X7 agonist ATP (P2X7-VS) or 10 min pretreatment with P2X7 antagonist AZ10606120 followed by stimulation with 3 mM ATP (AZ-VS) ( n = 5). D Size of PBS S-VS, P2X7-VS, and AZ-VS ( n = 5). E Number of vesicles released in 30 min from CT26 cells in DMSO vehicle (DMSO S-VS), following stimulation with P2X7 agonist ATP (P2X7-VS) or 10 min pretreatment with P2X7 antagonist A740003 followed by stimulation with 3 mM ATP (A74-VS) ( n = 7). F Size of DMSO- S-VS, P2X7-VS, and A74-VS ( n = 7). G Western blot for GM130, Alix, P2X7, CD39, CD73, and A2A in CT26 cells, S-VS and P2X7-VS. Pericellular ATP was measured with the pmeLUC probe expressed on the cell surface of untreated CT26 cells or after 5 min of exposure to PBS vehicle, S-VS, and P2X7-VS ( n = 4). H Quantification of luminescence changes was expressed as a fold increase on time 0. I Representative images of photon emissions. Changes in ATP J concentration increase on time 0 in the supernatants of CT26 cells, untreated or treated with PBS vehicle, S-VS, or P2X7-VS, measured with a luciferin/luciferase assay ( n = 3). Changes in adenosine K concentration increase on time 0 in the supernatants of CT26 cells untreated or treated with PBS vehicle, S-VS, P2X7-VS, or P2X7-VS plus 5uM CD73 inhibitor AB680 ( n = 5). * p < 0.05, ** p < 0.001, *** p < 0,0001, **** p < 0.00001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Staining, Confocal Microscopy, Activation Assay, Western Blot, Concentration Assay, Luciferase

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: Percentage of lung cells positive to P2X7 A and A2A F staining in mice injected intravenously with only CT26 Luc2 cells or CT26 Luc2 pre-treated with S-VS, P2X7-VS, and AZ-VS ( n = 3). Representative immunohistochemistry images of mice injected intravenously with CT26 Luc2 alone B , G or pre-treated with S-VS C , H , P2X7-VS D , I , or AZ-VS E , J . * p < 0.05, ** p < 0.001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Staining, Injection, Immunohistochemistry

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: Mice were injected intravenously with CT26 Luc2 cells and treated intraperitoneally with placebo, the P2X7 antagonist AZ10606120 (2 mg/Kg), the A2A antagonist SCH58261 (1 mg/Kg), or both drugs every three days. A Quantification of photon emission, expressed as total flux (p/s), on day 14 from the inoculum ( n = 6) B Representative images of photon emission at day 14 from the inoculum. C Area of metastasis expressed as a percentage of total lung area ( n = 6). Representative hematoxylin/eosin staining of lungs from mice treated with D placebo, E the P2X7 antagonist AZ10606120 (2 mg/Kg), F the A2A antagonist SCH58261 (1 mg/Kg), and G combination of the two drugs. Black arrows indicate metastatic lesions. Systemic levels of H IL-17 ( n = 6) and I IL-23 ( n = 4) were measured in the plasma of tumor-bearing mice. Systemic levels of J IL-17 ( n = 4) and K IL-23 ( n = 4) measured in the plasma of mice not injected with tumor cells but treated only with placebo, AZ10606120 (2 mg/Kg), SCH58261 (1 mg/Kg), or both compounds.* p < 0.05, ** p < 0.001, *** p < 0.0001, **** p < 0.00001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Injection, Staining, Clinical Proteomics

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: A–J BALB/c mice were injected intravenously with CT26 Luc2 cells and treated intraperitoneally with placebo, AZ10606120 (2 mg/Kg), SCH58261 (1 mg/Kg), or a combination of both drugs. Percentage of lung cells positive for P2X7 A and A2A F staining ( n = 4). Representative immunohistochemistry images of mice treated with placebo B , G , P2X7 antagonist AZ10606120 (C, H), A2A antagonist SCH58261 D , I , or both drugs E , J . * p < 0.05.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Injection, Staining, Immunohistochemistry

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: BALB/c mice were subcutaneously injected with CT26 and treated with placebo, AZ10606120 (2 mg/Kg), SCH58261 (1 mg/Kg) or both drugs ( n = 12). A Ex vivo tumor volume on day 14, and B representative images of tumors. C Systemic levels of the proinflammatory cytokine IL-17 ( n = 4). nude/nude mice were subcutaneously injected with HCT116 cells and treated i.p. with placebo, AZ10606120 (2 mg/Kg), SCH58261 (1 mg/Kg) or both drugs. D Ex vivo tumor volume at day 14 from the inoculum ( n = 6). E Representative tumor image. F HCT116 Luc2 were injected into the tail vein of nude/nude mice and treated with placebo, AZ10606120 (2 mg/Kg), SCH58261 (1 mg/Kg) or both drugs ( n = 7). Photon emission on day 14 total flux (p/s). G Image representative of data shown in F . * p < 0.05, ** p < 0.001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Injection, Ex Vivo

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: The mRNA expression of P2X7A A , B , P2X7B C , D , CD39 E , F , CD73 G , H , and A2A I , J was evaluated in the cDNAs of 158 patients with CRC subdivided into stage I ( n = 24), stage II ( n = 50), stage III ( n = 52), and stage IV ( n = 32) which comprised 11 samples derived from metastases in organs other than the colon. K Spearman’s correlation coefficient among P2X7A, P2X7B, CD39, CD73 , and A2A was evaluated in CRC metastatic patients. L Spearman’s correlation coefficient was evaluated between P2X7 and A2A expression in colon adenocarcinoma samples obtained from the Cancer Genome Atlas database. * p < 0.05, ** p < 0.01, *** p < 0.001. **** p < 0.0001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Expressing, Derivative Assay

Journal: Cell Death & Disease

Article Title: P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis

doi: 10.1038/s41419-025-07897-2

Figure Lengend Snippet: mRNA expression of A P2X7A , B P2X7B , C A2A , D CD39 , and E CD73 in CRC patients subdivided into APC WT and APC mutated groups ( n = 6). Percentage of cells positive for P2X7 F and A2A G in the colons of WT and PIRC rats and PIRC tumors ( n = 4). Representative images of immunohistochemical staining for P2X7 and A2A in the colon of WT 1-year rats H, K and in the normal colon I, L and the tumor mass J, M of 1-year PIRC rats. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: After five days, when tumor masses became evident, we started the treatment, which was repeated every 72 h, with an intraperitoneal (i.p.) injection of placebo (PBS + 0.002% DMSO), the P2X7 antagonist AZ10606120 (2 mg/Kg) (Tocris Bioscience), the A2A antagonist SCH58261 (1 mg/Kg) (Tocris Bioscience), and a combination of both antagonists.

Techniques: Expressing, Immunohistochemical staining, Staining

Journal: Frontiers in Pharmacology

Article Title: Microglial adenosine A 2A receptor in the paraventricular thalamic nucleus regulates pain sensation and analgesic effects independent of opioid and cannabinoid receptors

doi: 10.3389/fphar.2024.1467305

Figure Lengend Snippet: Pharmacological manipulation of PVT A 2A R regulates pain behaviors in mice. (A) Experimental timeline for cannula implantation, drug infusion (CGS21680 and SCH58261), and Von Frey and Hargreaves tests. (B) Diagram of injection cannula in the PVT region. (C, D) 50%PWTs (C) and PWLs (D) in mice treated with vehicle and CGS21680 (Vehicle, n = 11 mice; CGS21680, n = 11 mice). (E, F) 50%PWTs (E) and PWLs (F) in mice treated with vehicle and SCH58261. (Vehicle, n = 11 mice; 0.4 ng, n = 11 mice; 4 ng, n = 11 mice; 40 ng, n = 11 mice). * p < 0.05, ** p < 0.01. Data analyzed with unpaired t -test (C, D) , or one-way ANOVA followed by Tukey post-tests (E, F) . Error bars indicate SEM. PVT, paraventricular nucleus. D3V, Third ventricle. LV, Lateral ventricles.

Article Snippet: A 2A Rs agonist CGS21680 hydrochloride (MedChemExpress), A 2A Rs antagonist SCH58261 MedChemExpress) were firstly dissolved in DMSO, then diluted with 0.9% saline.

Techniques: Injection

Journal: Frontiers in Pharmacology

Article Title: Microglial adenosine A 2A receptor in the paraventricular thalamic nucleus regulates pain sensation and analgesic effects independent of opioid and cannabinoid receptors

doi: 10.3389/fphar.2024.1467305

Figure Lengend Snippet: PVT A 2A R antagonism alleviated CFA inflammatory pain. (A) Experimental timeline for cannula implantation, CFA or Saline (Sham) injection, drug infusion (SCH58261), and Von Frey and Hargreaves tests. (B, C) 50%PWTs and PWLs in Sham and CFA mice received vehicle or SCH58261 treatment at different time points following CFA injection. Von Frey test results show significantly increased mechanical pain threshold in 40 ng SCH58261-treated group compared to Vehicle group. (Sham Vehicle, n = 12 mice; Sham SCH, n = 11 mice; CFA_4h Vehicle, n = 15 mice; CFA_4h SCH, n = 16 mice; CFA_3d Vehicle, n = 10 mice; CFA_3d SCH, n = 8 mice). * p < 0.05, ** p < 0.01, *** p < 0.001. Data analyzed by (B, C) two-way ANOVA with Tukey post-tests. Error bars indicate SEM.

Article Snippet: A 2A Rs agonist CGS21680 hydrochloride (MedChemExpress), A 2A Rs antagonist SCH58261 MedChemExpress) were firstly dissolved in DMSO, then diluted with 0.9% saline.

Techniques: Saline, Injection