CPYPP

CPYPP is a DOCK2-Rac1 interaction inhibitor. CPYPP binds to DOCK2 DHR-2 domain and inhibits the guanine nucleotide exchange factor (GEF) activity of DOCK2^DHR-2 for Rac1 in a dose-dependent manner with an IC₅₀ of 22.8 µM. CPYPP also inhibits DOCK180 and DOCK5 and less inhibits DOCK9^[1]. IC50 & Target: IC50: 22.8 µM (GEF activity of DOCK2^DHR-2 for Rac1) In Vitro: CPYPP binds to DOCK2 DHR-2 domain in a reversible manner and inhibited its catalytic activity in vitro. When lymphocytes are treated with CPYPP, both chemokine receptor- and antigen receptor-mediated Rac activation are blocked, resulting in marked reduction of chemotactic response and T cell activation^[1].
Although overexpression of DOCK2 induces Rac activation in HEK293T cells, this activation is markedly suppressed by treating the cells with CPYPP at 100 µM for 1 hr before assay^[1]. In Vivo: When 2.5 mg/kg of CPYPP is administrated intravenously, the plasma concentration of CPYPP is only 2.4 µM at 30 min. However, by intraperitoneally injecting 250 mg/kg of CPYPP into mice, the plasma concentration of CPYPP reached to 11.3 µM at 30 min and 10.9 µM at 1 hr, respectively^[1].
The adoptively transferred spleen cells from mice that has been made by a ‘‘knock-in’’ strategy to express endogenous DOCK2 as a fusion protein with green fluorescent protein (GFP). Intraperitoneal injection of CPYPP (5 mg per mouse) 1 hr before adoptive transfer reduces the percentage of the migrated T cells to <25% of the control level^[1].