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| Drug class | antiplatelet drug |
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| Formula | C22H25N6O8P |
| Molar mass | 532.450 g·mol−1 |
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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 an experimental drug. It is classified as an antiplatelet medication. [1] It was under investigation for use in blood clotting problems, [2] as well as during coronary artery bypass surgery. [3]
Regrelor is available in an intravenous formulation. [1]
Regrelor is classified as a purinergic P2 receptor (P2Y12) antagonist. [4] Other compounds in the same mechanistic class include clopidogrel and ticagrelor. It is characterized as a reversible, competitive receptor antagonist. [5] The IC50 for antagonism of ADP-induced (P2Y12-mediated) platelet aggregation was 16 nM in vitro. [3]
Regrelor's primary metabolite is called INS51088. [5]
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 experiments in rats, 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]
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias.
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where anticoagulants have little effect.
Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy, in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring.
Ticlopidine, sold under the brand name Ticlid, is a medication used to reduce the risk of thrombotic strokes. It is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Research initially showed that it was useful for preventing strokes and coronary stent occlusions. However, because of its rare but serious side effects of neutropenia and thrombotic thrombocytopenic purpura it was primarily used in patients in whom aspirin was not tolerated, or in whom dual antiplatelet therapy was desirable. With the advent of newer and safer antiplatelet drugs such as clopidogrel and ticagrelor, its use remained limited.
Dipyridamole is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.
Prasugrel, sold under the brand name Effient in the US, Australia and India, and Efient in the EU) is a medication used to prevent formation of blood clots. It is a platelet inhibitor and an irreversible antagonist of P2Y12 ADP receptors and is of the thienopyridine drug class. It was developed by Daiichi Sankyo Co. and produced by Ube and marketed in the United States in cooperation with Eli Lilly and Company.
Tirofiban, sold under the brand name Aggrastat, is an antiplatelet medication. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibrinogen and the platelet integrin receptor GP IIb/IIIa and is the first drug candidate whose origins can be traced to a pharmacophore-based virtual screening lead.
P2Y12 is a chemoreceptor for adenosine diphosphate (ADP) that belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors. This P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. The P2Y12 receptor is involved in platelet aggregation and is thus a biological target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.
Vorapaxar is a thrombin receptor antagonist based on the natural product himbacine, discovered by Schering-Plough and developed by Merck & Co.
Seratrodast (development name, AA-2414; marketed originally as Bronica) is a thromboxane A2 (TXA2) receptor (TP receptor) antagonist used primarily in the treatment of asthma. It was the first TP receptor antagonist that was developed as an anti-asthmatic drug and received marketing approval in Japan in 1997. As of 2017 seratrodast was marketed as Bronica in Japan, and as Changnuo, Mai Xu Jia, Quan Kang Nuo in China.
Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. It blocks serotonin-induced platelet aggregation, and has applications in the treatment of many diseases including diabetes mellitus, Buerger's disease, Raynaud's disease, coronary artery disease, angina pectoris, and atherosclerosis.
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y12 receptor. The drug is produced by AstraZeneca.
Terutroban is an antiplatelet agent developed by Servier Laboratories. It is a selective thromboxane prostanoid (TP) antagonist and is an orally active drug in clinical development for the secondary prevention of acute thrombotic complications.
Thienopyridines are a class of selective, reversible ADP receptor/P2Y12 inhibitors used for their anti-platelet activity.
Cangrelor, sold under the brand name Kengreal in the United States, CANREAL in India ( MSN Labs ) and Kengrexal in the European Union) is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion.
Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute coronary syndrome (ACS) or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a stroke. These drugs antagonize the P2Y12 platelet receptors and therefore prevent the binding of ADP to the P2Y12 receptor. This leads to a decrease in aggregation of platelets, prohibiting thrombus formation. The P2Y12 receptor is a surface bound protein found on blood platelets. They belong to G protein-coupled purinergic receptors (GPCR) and are chemoreceptors for ADP.
Elinogrel (INN, USAN) was an experimental antiplatelet drug acting as a P2Y12 inhibitor. Similarly to ticagrelor and in contrast to clopidogrel, elinogrel was a reversible inhibitor that acted fast and short (for about 12 hours), and it was not a prodrug but pharmacologically active itself. The substance was used in form of its potassium salt, intravenously for acute treatment and orally for long-term treatment. Development was terminated in 2012.
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90's. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric and multi-mechanism inhibitors might lead the way to a safer anticoagulant.
Multiplate multiple electrode aggregometry (MEA) is a test of platelet function in whole blood. The test can be used to diagnose platelet disorders, monitor antiplatelet therapy, and is also investigated as a potential predictor of transfusion requirements and bleeding risk in cardiac surgery.
