A3R x TNF-α

Last update 08 May 2025

Basic Info

Related Targets

A3RTNF-α

Drugs associated with A3R x TNF-α

MDL-201449

Target

A3R x TNF-α

Mechanism

A3R agonists [+1]

Active Org.-

Originator Org.

Hoechst Marion Roussel, Inc.

Active Indication-

Inactive Indication

Colitis [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with A3R x TNF-α

100 Translational Medicine associated with A3R x TNF-α

0 Patents (Medical) associated with A3R x TNF-α

Literatures (Medical) associated with A3R x TNF-α

01 Mar 2025·Bioorganic & Medicinal Chemistry

An overview of small-molecule agents for the treatment of psoriasis

Review

Author: Jin, Zhiheng ; Yao, Hongliang ; He, Dengqin ; Chen, Jiaxin ; Zhang, Yali ; Li, Gang ; Li, Mengjie

Psoriasis is a prevalent, chronic inflammatory disease characterized by abnormal skin plaques. To date, physical therapy, topical therapy, systemic therapy and biologic drugs are the most commonly employed strategies for treating psoriasis. Recently, many agents have advanced to clinical trials, and some anti-psoriasis drugs have been approved, including antibody drugs and small-molecule drugs. Many antibody drugs targeting cytokines and receptors, such as interleukin (IL-17 and IL-23) and tumor necrosis factor-α (TNF-α), have been approved for the treatment of psoriasis. And numerous small-molecule agents have displayed promising activities in the treatment of psoriasis. The targets of anti-psoriasis drugs encompass phosphodiesterase IV (PDE4), Janus kinase (JAK), tyrosine kinase (TYK), retinoic acid-related orphan receptors (ROR), vitamin D receptor (VDR), Interleukin (IL), Aryl hydrocarbon receptor (AhR), Interleukin-1 receptor-associated kinase 4 (IRAK), chemoattractant-like receptor 1 (ChemR23), Sphingosine-1-phosphate receptor (S1P), A3 adenosine receptor (A3AR), Heat shock protein 90 (HSP90), The Rho-associated protein kinases (ROCK), The bromodomain and extra-terminal domain (BET), FMS-like tyrosine kinase 3 (FLT3), Tumor Necrosis Factor α Converting Enzyme (TACE), Toll-like receptors (TLR), NF-κB inducing kinase (NIK), DNA topoisomerase I (Topo I), among others. Herein, this review mainly recapitulates the advancements in the structure and enzyme activity of small-molecule anti-psoriasis agents over the last ten years, and their binding modes were also explored. Hopefully, this review will facilitate the development of novel small-molecule agents as potential anti-psoriasis drugs.

01 Jan 2025·Pain physician

Mode of Action of Amitriptyline Against Neuropathic Pain via Specific NF-kB Pathway Suppression.

Article

Author: Kwon, So Young ; Hwang, YouMi

BACKGROUNDNeuropathic pain occurs for various reasons involving adenosine receptors. One of several drugs used to control neuropathic pain is amitriptyline, a tricyclic antidepressant. Amitriptyline has an antinociceptive effect on the A3 adenosine receptor (A3AR). However, the exact mechanisms underlying A3AR activation remain unclear.OBJECTIVESBy investigating the effects of amitriptyline on neuropathic pain mitigation and its impact on inflammatory pathways via A3AR activation, we aimed to provide novel insights into the potential mechanisms of action of amitriptyline in neuropathic pain management. These insights could potentially revolutionize the way we understand and treat neuropathic pain.STUDY DESIGNWe used Sprague-Dawley rats for the neuropathic pain models. The rats were sorted into the sham (control), neuropathic pain (NP+NS), and neuropathic pain and amitriptyline (NP+AMI) groups. Each group consisted of 8 rats. This design allowed us to compare the effects of amitriptyline on neuropathic pain in a control group and a group that experienced neuropathic pain without amitriptyline treatment.SETTINGSt. Vincent's hospital, research institute of medical science.METHODSNormal saline and amitriptyline were injected intraperitoneally into rats using a subcutaneously implanted osmotic pump. A week after the procedure, nuclear factor kappa B (NF-kB) and a related proinflammatory cytokine (TNF-a) were quantified using immunoblotting or reverse-transcription PCR.RESULTSOur results brought positive news. The NF-kB concentrations of the groups were not different from one another, indicating a stable baseline. The control and NP+NS groups showed relatively increased activation of the mu-opioid receptor (MOR) and proinflammatory cytokines, including TNF-a, but demonstrated no intergroup difference. However, the MOR and TNF-a concentrations were markedly lower in the NP+AMI group than in the control or NP+NS groups (P = 0.02, 0.002, respectively). This difference suggests a potential for amitriptyline to reduce inflammation. The paw withdrawal threshold test revealed a recovery response to mechanical allodynia for the NP+AMI group (P < 0.05), indicating a positive impact on neuropathic pain.LIMITATIONSThe experiment involved only a few mice, so the results may not be generalizable.CONCLUSIONSThe release of proinflammatory cytokines via NF-kB expression and subsequent inflammatory responses is significantly associated with the development of neuropathic pain. Our study reveals that AMI effectively suppresses NF-kB-related proinflammatory cytokines, offering a promising avenue for treating pain related to peripheral nerve injuries. These findings provide valuable insights into neuropathic pain management.

01 Oct 2024·Purinergic Signalling

Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells

Article

Author: Gao, Zhan-Guo ; Jacobson, Kenneth A ; Hanover, John A ; Chen, Weiping ; Li, Jonathan ; Tosh, Dilip K ; Gao, Ray R

AbstractThe A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1β, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Important upstream regulators include IL-1a, IL-1β, TNF-α, NF-κB, etc. PPAR, which modulates eicosanoid metabolism, was highly downregulated by the A3AR agonist. Considering previous pharmacological results and mathematical modeling, LUF6000’s small enhancement of genetic upregulation suggested that MRS5698 is a nearly full agonist, which we demonstrated in both cAMP and calcium assays. The smaller effect of LUF6000 on MRS5698 in comparison to its effect on Cl-IB-MECA was shown in both HL-60 cells endogenously expressing the human (h) A3AR and in recombinant hA3AR-expressing CHO cells, consistent with its HL-60 cell genetic regulation patterns. In summary, by using both selective agonists and PAM, we identified genes that are closely relevant to immunity and inflammation to be regulated by A3AR in differentiated HL-60 cells, a cell model of neutrophil function. In addition, we demonstrated the previously uncharacterized allosteric signaling-enhancing effect of LUF6000 in cells endogenously expressing the hA3AR.

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