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J Clin Transl Sci. 2019 Jun;3(2-3):65-74. doi: 10.1017/cts.2019.382. Epub 2019 Jun 28.

Preclinical Studies of RUC-4, a Novel Platelet αIIbβ3 Antagonist, in Non-Human Primates and With Human Platelets.

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Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY, USA.
Biomere, Worcester, MA, USA.
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD.
Department of Biomedical and Pharmaceutical Sciences, Touro College of Pharmacy, New York NY, USA.



We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST Segment Elevated Myocardial Infarction (STEMI).


We studied the: 1. pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg IV, IM, and SC in non-human primates (NHPs); 2. impact of aspirin on RUC-4 IC50 in human platelet-rich plasma (PRP); 3. effect of different anticoagulants on the RUC-4 IC50 in human PRP; and 4. relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.


1. All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5-15 min, with T½ s between 0.28 and 0.56 hrs. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all 3 doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4-5 hours. 2. The RUC-4 IC50 for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs. 37±5 nM; p=0.39). 3. The RUC-4 IC50 was significantly higher in PRP prepared from PPACK-anticoagulated blood compared to citrate-anticoagulated blood using either TRAP (122±17 vs. 66±25 nM; p=0.05; n=4) or ADP (102±22 vs. 54±13; p<0.001; n=5). 4. There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.


Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.


Antiplatelet therapy; Integrin receptors; Platelets; ST segment elevation myocardial infarction (STEMI); αIIbβ3 antagonists

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