M351-0056 is an orally active VISTA agonist with a K d value of 12.60 μM. M351-0056 inhibits the activation of the JAK2 - STAT2 pathway, reduces the phosphorylation levels of JAK2 and STAT2, and regulates type I interferon ( IFN-I ) and non-canonical NF-κB pathways. M351-0056 decreases the levels of cytokines ( IFN-γ, IL-17A, TNF-α, IL-2 and IL-1β). M351-0056 improves imiquimod -induced psoriasis-like skin inflammation, reduces autoantibody levels, kidney damage and immune cell expansion in mice susceptible to chronic graft-versus-host disease and lupus, and delays the progression of systemic lupus erythematosus. M351-0056 can be used in research related to psoriasis-like dermatitis and systemic lupus erythematosus [1] [2].
In Vivo, M351-0056 (25 mg/kg; p.o.; daily; 6 days) ameliorates Imiquimod -induced psoriasis-like skin inflammation in BALB/c mice, reducing ear acanthosis by 37.5% and lowering key pro-inflammatory cytokine levels in serum and skin tissue[1]. M351-0056 (50 mg/kg/day; i.g.; daily; 28 days) attenuates systemic lupus erythematosus in cGVHD mice via reducing renal dysfunction, autoantibody levels, renal pathology, and activation of IFN-I and noncanonical NF-κB pathways[2]. M351-0056 (50 mg/kg/day; i.g.; daily; 42 days) alleviates spontaneous systemic lupus erythematosus in MRL/lpr mice by reducing lymphoid organ enlargement, renal dysfunction, autoantibody levels, renal pathology, immune cell activation, and activation of IFN-I and noncanonical NF-κB pathways[2].
In Vitro, M351-0056 (serial dilution; 30 min) binds to purified hVISTA-ECD protein with a KD value of 12.60 μM[1]. M351-0056 (5-50 μM; 48 h) enhances VISTA-mediated inhibition of IFN-γ, IL-17A, TNF-α and IL-2 secretion in activated peripheral blood mononuclear cells (PBMCs), with the strongest effect observed at 50 μM after 48 h[1]. M351-0056 (10 μM) enhances VISTA-mediated conversion of peripheral blood mononuclear cells (PBMCs) into CD4+Foxp3+ regulatory T cells[1]. M351-0056 (25-50 μM; 48 h) enhances the inhibitory effect of VISTA on IL-2 secretion in Jurkat E6.1 cells stimulated with PHA /PMA, with significant effects observed after treatment at concentrations of 25 μM and 50 μM for 48 h[1]. M351-0056 regulates the function of VISTA in peripheral blood mononuclear cells (PBMC) by reducing the mRNA expression of key genes in the JAK2-STAT2 signaling pathway[1]. M351-0056 inhibits cytokine production in Jurkat cells[2].
References:
[1]. Hu X, et al. M351-0056 is a novel low MW compound modulating the actions of the immune-checkpoint protein VISTA. Br J Pharmacol. 2021 Mar;178(6):1445-1458.
[2]. Yang L, et al. Imatinib and M351-0056 enhance the function of VISTA and ameliorate the development of SLE via IFN-I and noncanonical NF-κB pathway. Cell biology and toxicology. 2023 Dec;39(6):3287-3304.
In Vivo, M351-0056 (25 mg/kg; p.o.; daily; 6 days) ameliorates Imiquimod -induced psoriasis-like skin inflammation in BALB/c mice, reducing ear acanthosis by 37.5% and lowering key pro-inflammatory cytokine levels in serum and skin tissue[1]. M351-0056 (50 mg/kg/day; i.g.; daily; 28 days) attenuates systemic lupus erythematosus in cGVHD mice via reducing renal dysfunction, autoantibody levels, renal pathology, and activation of IFN-I and noncanonical NF-κB pathways[2]. M351-0056 (50 mg/kg/day; i.g.; daily; 42 days) alleviates spontaneous systemic lupus erythematosus in MRL/lpr mice by reducing lymphoid organ enlargement, renal dysfunction, autoantibody levels, renal pathology, immune cell activation, and activation of IFN-I and noncanonical NF-κB pathways[2].
In Vitro, M351-0056 (serial dilution; 30 min) binds to purified hVISTA-ECD protein with a KD value of 12.60 μM[1]. M351-0056 (5-50 μM; 48 h) enhances VISTA-mediated inhibition of IFN-γ, IL-17A, TNF-α and IL-2 secretion in activated peripheral blood mononuclear cells (PBMCs), with the strongest effect observed at 50 μM after 48 h[1]. M351-0056 (10 μM) enhances VISTA-mediated conversion of peripheral blood mononuclear cells (PBMCs) into CD4+Foxp3+ regulatory T cells[1]. M351-0056 (25-50 μM; 48 h) enhances the inhibitory effect of VISTA on IL-2 secretion in Jurkat E6.1 cells stimulated with PHA /PMA, with significant effects observed after treatment at concentrations of 25 μM and 50 μM for 48 h[1]. M351-0056 regulates the function of VISTA in peripheral blood mononuclear cells (PBMC) by reducing the mRNA expression of key genes in the JAK2-STAT2 signaling pathway[1]. M351-0056 inhibits cytokine production in Jurkat cells[2].
References:
[1]. Hu X, et al. M351-0056 is a novel low MW compound modulating the actions of the immune-checkpoint protein VISTA. Br J Pharmacol. 2021 Mar;178(6):1445-1458.
[2]. Yang L, et al. Imatinib and M351-0056 enhance the function of VISTA and ameliorate the development of SLE via IFN-I and noncanonical NF-κB pathway. Cell biology and toxicology. 2023 Dec;39(6):3287-3304.