Regrelor (also known as INS50589) is an experimental

antiplatelet drug 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 effecti ...

that was under investigation by

Merck Sharp and Dohme Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp ...

in human clinical trials. Although it was initially found to be well tolerated in healthy subjects, safety concerns led to cessation of clinical trials.

Medical uses

Regrelor is an experimental drug. It is classified as an antiplatelet medication. It was under investigation for use in

blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...

problems, as well as during coronary artery bypass surgery.

Available forms

Regrelor is available in an intravenous formulation.

Pharmacology

Regrelor is classified as a purinergic P2 receptor (P2Y₁₂) antagonist. Other compounds in the same mechanistic class include

clopidogrel Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following ...

and

ticagrelor 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 ...

. It is characterized as a reversible,

competitive Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indivi ...

receptor antagonist. The

IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...

for antagonism of ADP-induced (P2Y₁₂-mediated) platelet aggregation was 16 nM ''in vitro''. Regrelor's

primary metabolite A primary metabolite is a kind of metabolite that is directly involved in normal growth, development, and reproduction. It usually performs a physiological function in the organism (i.e. an intrinsic function). A primary metabolite is typically pr ...

is called INS51088.

Chemistry

Regrelor is structurally similar to

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, just like

. Regrelor has 4 hydrogen bond donors and 11 acceptors. It is produced as a di

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

salt. The two

atoms bind the negatively charged

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

moiety in solution.

Synthesis

Regrelor was synthesized from adenosine diphosphate (ADP), an endogenous chemical involved in

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

. The authors noted that the addition of a lipophilic moiety like

cinnamaldehyde Cinnamaldehyde is an organic compound with the formula(C9H8O) C6H5CH=CHCHO. Occurring naturally as predominantly the ''trans'' (''E'') isomer, it gives cinnamon its flavor and odor. It is a phenylpropanoid that is naturally synthesized by the sh ...

at the C-2' and C-3' positions, combined with ethylurea at N-6 on the

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its deri ...

base, yielded regrelor.

History

Regrelor was developed around the same time as

prasugrel 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 ...

and

cangrelor 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 P ...

. After Inspire Pharmaceuticals initially developed the drug, it was purchased by Merck Sharp and Dohme.

Research

Pre-clinical experiments in

rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...

, dogs, and monkeys found that the drug acted quickly to inhibit platelet aggregation, and that baseline function was restored quickly after discontinuation of treatment. In a

phase 1 clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

sponsored by Merck Sharp and Dohme Corporation, regrelor was well tolerated in healthy volunteers. In 2008, phase 2 trials were discontinued. It is believed that further development of the drug was ceased due to safety reasons. In the trial, there was an increased risk of

bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

for patients on regrelor.

References

{{Reflist, 30em Antiplatelet drugs