Regrelor (also known as INS50589) is an experimental antiplatelet drug that was under investigation by Merck Sharp and Dohme in human clinical trials. Although it was initially found to be well tolerated in healthy subjects, safety concerns led to cessation of clinical trials.
Regrelor is structurally similar to AMP, just like ticagrelor.[3] Regrelor has 4 hydrogen bond donors and 11 acceptors.[4] It is produced as a disodium salt.[6] The two sodium atoms bind the negatively charged phosphate moiety in solution.[3]
Regrelor was synthesized from adenosine diphosphate (ADP), an endogenous chemical involved in metabolism.[7] The authors noted that the addition of a lipophilic moiety like cinnamaldehyde at the C-2' and C-3' positions, combined with ethylurea at N-6 on the adenine base, yielded regrelor.[8]
Regrelor was developed around the same time as prasugrel and cangrelor.[1] After Inspire Pharmaceuticals initially developed the drug, it was purchased by Merck Sharp and Dohme.[6]
Pre-clinical experimentsinrats, dogs, and monkeys found that the drug acted quickly to inhibit platelet aggregation, and that baseline function was restored quickly after discontinuation of treatment.[5]
In a phase 1 clinical trial sponsored by Merck Sharp and Dohme Corporation, regrelor was well tolerated in healthy volunteers.[9][5] In 2008, phase 2 trials were discontinued.[2] It is believed that further development of the drug was ceased due to safety reasons.[6] In the trial, there was an increased risk of bleeding for patients on regrelor.[3]
^ ab"Regrelor". Adis Insight. Springer International Publishing AG. Retrieved 3 August 2017.
^ abcdeChackalamannil S, Rotella D, Ward S (3 June 2017). Comprehensive Medicinal Chemistry (III ed.). Elsevier. p. 568. ISBN978-0-12-803201-5.
^ ab"Regrelor". PubChem. National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine. Retrieved 3 August 2017.
^ abcdJohnson FL, Boyer JL, Leese PT, Crean C, Krishnamoorthy R, Durham T, et al. (August 2007). "Rapid and reversible modulation of platelet function in man by a novel P2Y(12) ADP-receptor antagonist, INS50589". Platelets. 18 (5): 346–56. doi:10.1080/09537100701268741. PMID17654304. S2CID31681877.
^Nave CR (2005). "Adenosine Triphosphate". Hyper Physics [serial on the Internet]. Georgia State University.
^Douglass JG, Patel RI, Yerxa BR, Shaver SR, Watson PS, Bednarski K, et al. (February 2008). "Lipophilic modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor". Journal of Medicinal Chemistry. 51 (4): 1007–25. doi:10.1021/jm701348d. PMID18232657.
^Clinical trial number NCT00099450 for "Study of the Tolerability, Pharmacokinetics, and Pharmacodynamics of INS50589 Intravenous Infusion in Healthy Volunteers" at ClinicalTrials.gov
