CPYPP is a DOCK2 inhibitor which bounds to DOCK2 DHR-2 domain in a reversible manner and inhibited its catalytic activity in vitro. It also inhibits DOCK1 and DOCK5 and exhibits selectivity over DOCK9.
DOCK2 is an atypical Rac activator predominantly expressed in hematopoietic cells. CPYPP is a small-molecule inhibitor of DOCK2. It dose-dependently inhibited the nucleotide exchange factor activity of DOCK2DHR-2 for Rac1 with an IC50 value of 22.8±2.4μM. DOCK2 overexpression-induced activation of Rac in HEK293T cells was significantly suppressed by one-hour pretreatment with CPYPP (100μM). Pretreatment of T cells or B cells with CPYPP at a concentration of 100μM for one hour almost completely inhibited Rac activation in response to CCL21 or CXCL13, respectively. One-hour treatment with CPYPP at 100μM inhibited TCR-mediated Rac activation in T cells. Treatment with 100μM CPYPP severely impaired CpG-A-induced Rac activation in pDCs. Intraperitoneal administration of mice with 5mg of CPYPP one hour before adoptive transfer reduced the percentage of migrated T cells to < 25% as compared to the control group[1].
作用机制
CPYPP is a small-molecule inhibitor of DOCK2 that reversibly binds to the DOCK2 DHR-2 domain and inhibited catalytic activity of DOCK2 in vitro[1].
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