The chemokine receptor CCR5 plays a crucial role in transmission of HIV isolates, which predominate in the early and middle stages of infection. DAPTA is a non-toxic experimental antiviral entry inhibitor by selectively targeting CCR5 with potent anti-HIV activities. DAPTA potently inhibited specific CD4-dependent binding of gp120 Bal and CM235 to CCR5 with IC50s of 0.06 nM and 0.32 nM, respectively. DAPTA inhibited the binding of gp120BaL/sCD4 to CCR5 in Cf2Th/synR5 cells with an IC50 of 55 pM. In immunoprecipitation assay, DAPTA (1 nM) blocked the formation of gp120/sCD4 complex with CCR5[1]. DAPTA increased the Th2 cytokines IL-4, IL-10, and IL-13 and induced a potent virostatic state in infected macrophages in vitro, as well as inhibited production of the proinflammatory cytokines IL-1 and TNFα, which upregulate virus expression[2].
DAPTA 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
0.1 mM
6 hours
DAPTA significantly reduced CSE-induced tight junction injury and inhibited the downregulation of ZO-1, occludin, CCL3, and CCR5 expression by CSE.
Front Pharmacol. 2021 Apr 19;12:551839.
16-HBE cells
0.1 mM
6 hours
DAPTA significantly reduced CSE-induced tight junction injury and inhibited the downregulation of ZO-1, occludin, CCL3, and CCR5 expression by CSE.
Front Pharmacol. 2021 Apr 19;12:551839.
DAPTA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SJL/J mice
Experimental autoimmune encephalomyelitis (EAE) model
Intraperitoneal injection
0.01 mg/kg
Once daily from day 14 to day 42 after immunization
To evaluate the therapeutic potential of DAPTA in EAE mice, results showed that DAPTA significantly reduced the expression of NF-κB p65, Notch-1, Notch-3, GM-CSF, MCP-1, iNOS, and TNF-α, while increasing the expression of IκBα.
Biomedicines. 2023 May 23;11(6):1511
SJL/J mice
Experimental autoimmune encephalomyelitis (EAE) model
Intraperitoneal injection
0.01 mg/kg
Once daily from day 14 to day 42
DAPTA treatment significantly reduced the expression of NF-κB p65, Notch-1, Notch-3, GM-CSF, MCP-1, iNOS, and TNF-α in EAE mice, while increasing the expression of IκBα.
Biomedicines. 2023 May 23;11(6):1511
C57BL/6 mice
CSE-induced COPD Mice model
Subcutaneous injection
10 μg/kg
Once daily for 6 weeks
DAPTA partially reversed the negative effects of CSE on lung function and tight junction protein expression in mice, reducing alveolar space enlargement and inflammatory responses.
Front Pharmacol. 2021 Apr 19;12:551839.
ApoE−/− mice
Atherosclerosis model
Tail vein injection
370 kBq
1, 4, and 24 hours
To evaluate the pharmacokinetics and targeting efficiency of DAPTA-Comb nanoparticles in an atherosclerosis model. Results showed extended blood circulation of 10%, 25%, and 40% DAPTA-Comb, with 40% DAPTA-Comb demonstrating higher plaque targeting efficiency.
Mol Pharm. 2021 Mar 1;18(3):1386-1396
Sprague-Dawley rats
Conscious adult and juvenile rats
Intracerebroventricular (ICV) administration
400 ng (acute), 2 ng (chronic)
Acute: single injection; chronic: twice daily for 5 days
To investigate the effect of gp120 on GH release and body weight, results showed gp120 significantly suppressed GH release and caused weight loss
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1927-32
United States, District of Col... 展开 >>umbia
Whitman Walker Clinic
Recruiting
Washington, District of Columbia, United States, 20009
Principal Investigator: Richard Elion, MD 收起 <<
United States, District of Col... 展开 >>umbia
Whitman Walker Clinic
Recruiting
Washington, District of Columbia, United States, 20009
Principal Investigator: Richard Elion, MD 收起 <<
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