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].
CPYPP 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SAS-DTX
10 µM
24 h
Induced cytoplasmic vacuolization and suppressed cell viability
Cell Biosci. 2024 Jun 10;14(1):78
OECM1-DTX
10 µM
24 h
Induced cytoplasmic vacuolization and suppressed cell viability
Cell Biosci. 2024 Jun 10;14(1):78
NCI-H1299
10 µM
24 h
Induced cytoplasmic vacuolization and cell death
Cell Biosci. 2024 Jun 10;14(1):78
PANC-1
10 µM
24 h
Induced cytoplasmic vacuolization and cell death
Cell Biosci. 2024 Jun 10;14(1):78
U-87 MG
10 µM
24 h
Induced cytoplasmic vacuolization and cell death
Cell Biosci. 2024 Jun 10;14(1):78
DBTRG-05MG
10 µM
24 h
Induced cytoplasmic vacuolization and cell death
Cell Biosci. 2024 Jun 10;14(1):78
MDA-MB-435
10 µM
24 h
Induced cytoplasmic vacuolization and cell death, inhibited cell proliferation and clonogenic activity
Cell Biosci. 2024 Jun 10;14(1):78
MDA-MB-231
10 µM
24 h
Induced cytoplasmic vacuolization and cell death, inhibited cell proliferation and clonogenic activity
Cell Biosci. 2024 Jun 10;14(1):78
human peripheral blood neutrophils
100 μM
60 min
inhibited fMLF-induced Rac2 activation, chemotaxis, and ROS production
J Immunol. 2014 Dec 1;193(11):5660-7
RCC7T/E
1–100μM
24 h
Measure cell viability, EC50 was 16μM
Prostate. 2020 Sep;80(13):1045-1057
VCaP
1–100μM
24 h
Measure cell viability, EC50 was 31–35μM
Prostate. 2020 Sep;80(13):1045-1057
MDA-PCa2b
1–100μM
24 h
Measure cell viability, EC50 was 31–35μM
Prostate. 2020 Sep;80(13):1045-1057
CD3+ T cells
100 μM
2 h
To evaluate the effect of CPYPP on chemotaxis of CD3+ T cells under CXCL12 stimulation. Results showed that CPYPP significantly inhibited CXCL12-induced chemotaxis (FC=0.57, P=1.0×10−7).
Nature. 2022 Sep;609(7928):754-760
pDCs
100 μM
12 h
To evaluate the effect of CPYPP on IFNα production by pDCs under CpG stimulation. Results showed that CPYPP significantly reduced IFNα production (FC=5.5×10−5, P=0.0038).
Nature. 2022 Sep;609(7928):754-760
CPYPP 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID mice
Breast cancer orthotopic xenograft model
Intraperitoneal injection
30 mg/kg
Daily for 14 days
Significantly suppressed tumor growth and induced tumor cell vacuolization
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