CXCR3 Inhibitor

AMG 487 is an orally active and selective antagonist of CXC chemokine receptor 3 (CXCR3) which inhibits the binding of CXCL10 and CXCL11 to CXCR3 with IC₅₀s of 8.0 and 8.2 nM, respectively.

Cyclazosin is an α₁D-adrenergic receptor antagonist and a partial agonist of CXCR4/ACKR3. The pKi values of Cyclazosin for cloned human α₁D, α₁B and α₁A adrenergic receptors are 9.28, 9.23 and 8.18, respectively. Cyclazosin induces β-arrestin recruitment in CXCR4 and ACKR3 with EC50 values of 16 μM and 10 μM, respectively, stimulates ERK1/2 phosphorylation, and induces receptor internalization. Cyclazosin potently inhibits CXCL12-induced chemotaxis of primary human aortic vascular smooth muscle cells. Cyclazosin alters MDMA-induced thermoregulatory responses in mice, converting monophasic hyperthermia to a biphasic pattern without affecting resting core body temperature. Cyclazosin can be used for diseases related to tumor metastasis, MDMA-induced hyperthermia and vasoconstriction.

Sirt1/CXCR3-IN-1 is a dual Sirt1/CXCR3 inhibitor with an IC₅₀ of 0.77 μM against Sirt1. Sirt1/CXCR3-IN-1 inhibits dengue virus replication, upregulates the expression of interferon-stimulated genes, and enhances the antiviral defense capacity of the host. Sirt1/CXCR3-IN-1 suppresses CXCR3-mediated T cell chemotaxis and cytokine release, thereby reducing immune activation and inflammatory responses. Sirt1/CXCR3-IN-1 is applicable to research related to dengue virus infection.

Anti-Mouse CXCR3/CD183 Antibody (CXCR3-173) is an anti-mouse CXCR3/CD183 IgG monoclonal antibody. Anti-Mouse CXCR3/CD183 Antibody (CXCR3-173) weakens the immune response by reducing the infiltration of CD4⁺ and CD8⁺ T cells. Anti-Mouse CXCR3/CD183 Antibody (CXCR3-173) significantly prolongs the survival time of heart or islet transplants in mice. Anti-Mouse CXCR3/CD183 Antibody (CXCR3-173) can be used for researches on immunology and cancer such as pancreatic cancer.

Olopatadine hydrochloride (ALO4943A; KW4679) is an orally active histamine H1 receptor antagonist and mast cell stabilizer. Olopatadine hydrochloride exerts antiallergic effects by blocking histamine H1 receptor-mediated activities. Olopatadine hydrochloride inhibits exocytosis, chemokine release, F-actin polymerization, CXCL10-induced calcium influx, and T cell chemotactic activity. Olopatadine hydrochloride also reduces the expression levels of CXCR3 on the surface of CD4⁺ and CD8⁺ T cells. Olopatadine hydrochloride inhibits scratching behavior, improves dermatitis scores, and suppresses intraepidermal neurite outgrowth. Olopatadine hydrochloride simultaneously decreases the levels of inflammatory markers, growth factors, histamine, and specific IgE, while increasing the expression of ErbB3A/HER3A. Olopatadine hydrochloride can be used in research related to seasonal pollinosis, chronic rhinitis, urticaria, allergic conjunctivitis, alopecia areata, and atopic dermatitis.

SCH-900875 is an orally active, brain-penetrant and selective CXCR3 receptor inhibitor, which also shows high selectivity over CXCR1 and CXCR2 receptors. SCH-900875 binds to CXCR3, blocking the binding of ligands CXCL9, CXCL10, and CXCL11, inhibiting downstream G protein and β-arrestin signaling pathways to suppress inflammatory cell migration. SCH-900875 is promising for research of autoimmune diseases (rheumatoid arthritis, multiple sclerosis) and inflammatory disorders (psoriasis, inflammatory bowel disease).