DT-678 inhibits platelet activation with lower tendency for bleeding compared to existing P2Y12 antagonists

Pharmacology Research & Perspectives
Dale A LauverHaoming Zhang

Abstract

The novel clopidogrel conjugate, DT-678, is an effective inhibitor of platelets and thrombosis in preclinical studies. However, a comparison of the bleeding risk with DT-678 and currently approved P2Y12 antagonists has yet to be determined. The objective of this study was to evaluate the bleeding tendency of animals treated with clopidogrel, ticagrelor, and DT-678. Ninety-one New Zealand white rabbits were randomized to one of 13 treatment groups (n = 7). Platelet activation was assessed by flow cytometry and light transmission aggregometry before and after the administration of various doses of DT-678, clopidogrel, and ticagrelor. Tongue template bleeding times were also measured before and after drug treatment. Treatment with P2Y12 receptor antagonists caused a dose-dependent reduction in markers of platelet activation (P-selectin and integrin αIIbβ3) and aggregation in response to adenosine diphosphate stimulation. At the same doses required for platelet inhibition, clopidogrel and ticagrelor significantly prolonged bleeding times, while DT-678 did not. DT-678 and the FDA-approved P2Y12 antagonists clopidogrel and ticagrelor are effective inhibitors of platelet activation and aggregation. However, unlike clopidogrel and tica...Continue Reading

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Citations

May 7, 2020·The Cochrane Database of Systematic Reviews·Carla PerrottaJorge Ramos
Apr 10, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Yifang SunDaniel T Eitzman

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Methods Mentioned

BETA
blood collection
flow cytometry
blood drawn

Software Mentioned

CFlow Plus
GraphPad
GraphPad Prism

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