ADWX 1 TFA is a new peptide inhibitor that is potent and selective for Kv1.3 with an IC50 value of 1.89 pM. ADWX 1 inhibits Kv1.3 channel activity specifically to inhibit both the initial calcium signaling and NF-κB activation. ADWX 1 TFA ameliorates the disease in rats of experimental autoimmune encephalomyelitis (EAE) models. ADWX 1 TFA can be used to study T cell-mediated autoimmune diseases [1] [2].
In Vivo, ADWX 1 (100 μg/kg/day, s.c., 3 days) ameliorates the disease through the inhibition of IL-2 and IFN-γ productions and CCR7- TEM proliferation in experimental autoimmune encephalomyelitis (EAE) of Sprague-Dawley rats[2]. ADWX 1 (5/10 mg/kg, s.c., 2 weeks) induces no pathological changes in the behavior or tissues of the rats (acute toxicity assay)[2].
In Vitro, ADWX 1 (1,10 nM, 1 h) TFA inhibits IL-2 and IFN-γ productions, and inhibits humans CD4+ CCR7- TEM cells activation selectively[2]. ADWX 1 (1,10 nM, 50 min) TFA reduces [Ca2+] in activated CD4+ CCR7- TCM cells from EAE rats[2]. ADWX 1 (1,10 nM, 1 h) TFA reduces NF-κB activation and suppresses Kv1.3 expression at both mRNA and protein levels preferentially in myelin basic protein (MBP) -stimulated CD4+ CCR7- T cells from EAE rats[2]. ADWX 1 (1,10 nM, 3 days) TFA suppresses Th17 activation but not differentiation in CD4+ CCR7- T cells[2].
References:
[1]. Han S, et al. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease. J Biol Chem. 2008 Jul 4;283(27):19058-65.
[2]. Li Z, et al. Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model. J Biol Chem. 2012 Aug 24;287(35):29479-94.
In Vivo, ADWX 1 (100 μg/kg/day, s.c., 3 days) ameliorates the disease through the inhibition of IL-2 and IFN-γ productions and CCR7- TEM proliferation in experimental autoimmune encephalomyelitis (EAE) of Sprague-Dawley rats[2]. ADWX 1 (5/10 mg/kg, s.c., 2 weeks) induces no pathological changes in the behavior or tissues of the rats (acute toxicity assay)[2].
In Vitro, ADWX 1 (1,10 nM, 1 h) TFA inhibits IL-2 and IFN-γ productions, and inhibits humans CD4+ CCR7- TEM cells activation selectively[2]. ADWX 1 (1,10 nM, 50 min) TFA reduces [Ca2+] in activated CD4+ CCR7- TCM cells from EAE rats[2]. ADWX 1 (1,10 nM, 1 h) TFA reduces NF-κB activation and suppresses Kv1.3 expression at both mRNA and protein levels preferentially in myelin basic protein (MBP) -stimulated CD4+ CCR7- T cells from EAE rats[2]. ADWX 1 (1,10 nM, 3 days) TFA suppresses Th17 activation but not differentiation in CD4+ CCR7- T cells[2].
References:
[1]. Han S, et al. Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease. J Biol Chem. 2008 Jul 4;283(27):19058-65.
[2]. Li Z, et al. Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model. J Biol Chem. 2012 Aug 24;287(35):29479-94.