SYN1436 is a selective human neonatal Fc receptor ( hFcRn ) antagonist with an IC50 of 2.4 nM. SYN1436 binds to hFcRn and inhibits hFcRn-hIgG interaction. SYN1436 can be used for the research of autoimmune diseases [1].
In Vivo, SYN1436 (0.5-10 mg/kg; i.v.; once daily; 4 days) increases hIgG catabolism in human FcRn transgenic mice in a dose-dependent manner, with the 10 mg/kg dose reducing hIgG levels by 90% and shortening hIgG half-life to 34 h[1]. SYN1436 (1-5 mg/kg; s.c. or i.v.; once weekly or three times weekly; up to 4 weeks) dose-dependently reduces endogenous serum IgG levels in cynomolgus monkeys without altering albumin, IgM, or IgA levels[1].
In Vitro, SYN1436 (2.4 nM; 2 h) potently inhibits the hIgG-shFcRn interaction in an ELISA format at pH 6, with an IC50 of 2.4 nM[1]. SYN1436 (2.8 nM; 1 h) potently inhibits hIgG binding to hFcRn-expressing 293c11 cells in a FACS-based competition assay at pH 6, with an IC50 of 2.8 nM[1]. SYN1436 (0.04-20 nM) binds with extremely high affinity to immobilized shFcRn at both pH 6 and pH 7.4, with Kd values of <0.5 nM and <0.8 nM, respectively[1]. SYN1436 does not inhibit the shFcRn-HSA interaction at pH 6 at a concentration of 10 μM, nor does it bind directly to HSA at concentrations up to 100 μM at pH 6 or pH 7.4[1].
References:
[1]. Mezo AR, et al. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2337-42.
In Vivo, SYN1436 (0.5-10 mg/kg; i.v.; once daily; 4 days) increases hIgG catabolism in human FcRn transgenic mice in a dose-dependent manner, with the 10 mg/kg dose reducing hIgG levels by 90% and shortening hIgG half-life to 34 h[1]. SYN1436 (1-5 mg/kg; s.c. or i.v.; once weekly or three times weekly; up to 4 weeks) dose-dependently reduces endogenous serum IgG levels in cynomolgus monkeys without altering albumin, IgM, or IgA levels[1].
In Vitro, SYN1436 (2.4 nM; 2 h) potently inhibits the hIgG-shFcRn interaction in an ELISA format at pH 6, with an IC50 of 2.4 nM[1]. SYN1436 (2.8 nM; 1 h) potently inhibits hIgG binding to hFcRn-expressing 293c11 cells in a FACS-based competition assay at pH 6, with an IC50 of 2.8 nM[1]. SYN1436 (0.04-20 nM) binds with extremely high affinity to immobilized shFcRn at both pH 6 and pH 7.4, with Kd values of <0.5 nM and <0.8 nM, respectively[1]. SYN1436 does not inhibit the shFcRn-HSA interaction at pH 6 at a concentration of 10 μM, nor does it bind directly to HSA at concentrations up to 100 μM at pH 6 or pH 7.4[1].
References:
[1]. Mezo AR, et al. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2337-42.