Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor

Beavers, Craig J.; Effoe, S. Aaron; Dobesh, Paul P.

doi:10.1097/fjc.0000000000001079

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…Selatogrel, a novel, potent, reversible, and selective 2-phenylprimdine-4-carboxamide that is subcutaneously administered is under development. The results from preclinical, phase 1, and phase 2 trials have confirmed that the agent provides sustained and reversible P2Y12 platelet inhibition with an acceptable safety profile and with a larger therapeutic window compared with the oral P2Y12 inhibitors [90,91].…”

Section: Selatogrelmentioning

confidence: 89%

Evolving Diagnostic and Management Advances in Coronary Heart Disease

Ribeiro

Correia

Oliveira

et al. 2023

Life

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Despite considerable improvement in diagnostic modalities and therapeutic options over the last few decades, the global burden of ischemic heart disease is steadily rising, remaining a major cause of death worldwide. Thus, new strategies are needed to lessen cardiovascular events. Researchers in different areas such as biotechnology and tissue engineering have developed novel therapeutic strategies such as stem cells, nanotechnology, and robotic surgery, among others (3D printing and drugs). In addition, advances in bioengineering have led to the emergence of new diagnostic and prognostic techniques, such as quantitative flow ratio (QFR), and biomarkers for atherosclerosis. In this review, we explore novel diagnostic invasive and noninvasive modalities that allow a more detailed characterization of coronary disease. We delve into new technological revascularization procedures and pharmacological agents that target several residual cardiovascular risks, including inflammatory, thrombotic, and metabolic pathways.

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Section: Selatogrelmentioning

confidence: 89%

Evolving Diagnostic and Management Advances in Coronary Heart Disease

Ribeiro

Correia

Oliveira

et al. 2023

Life

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“…Non-nucleotide antagonists include the analogue of reactive blue 2, PSB-0739 Table 6 , [ 11 , 67 ], 6-amino-2-thio-3H-pyrimidin-4-one derivatives [ 38 ], ethyl 6-aminonicotinate acyl sulfonamides [ 8 ], flavonolignans [ 18 ], morpholine derivatives [ 3 ], piperazinyl glutamates [ 130 , 167 ], as well as salvianolic acids [ 101 ]. Selatogrel (ACT-246475) has a nanomolar affinity at the human P2Y 12 receptor [ 9 ] and can be applied by subcutaneous administration [ 14 , 147 ]. Selatogrel may act as inverse agonist at the human P2Y 12 receptor [ 132 ].…”

Section: P2y 12 Receptor Ligandsmentioning

confidence: 99%

Pharmacological characterization of P2Y receptor subtypes – an update

von Kügelgen

2023

Purinergic Signalling

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P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. There are eight mammalian P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14). The widely expressed P2Y receptors play important roles in physiology and pathophysiology. This review summarizes the use of pharmacological tools to characterize the P2Y receptor subtypes involved in these responses. MRS2500 is a potent and selective antagonist acting at the P2Y1 receptor. AR-C118925 is useful for the selective antagonism of the P2Y2 receptor. PSB16133 blocks the P2Y4 receptor, MRS2578 is an antagonist at the P2Y6 receptor and NF157 as well as NF340 block the P2Y11 receptor. ADP-induced platelet aggregation is mediated by P2Y1 and P2Y12 receptors. A number of compounds or their active metabolites reduce ADP-induced platelet aggregation by blocking the P2Y12 receptor. These include the active metabolites of the thienopyridine compounds clopidogrel and prasugrel, the nucleoside analogue ticagrelor and the nucleotide analogue cangrelor. PSB0739 is also a potent antagonist at the P2Y12 receptor useful for both in vitro and in vivo studies. MRS2211 and MRS2603 inhibit P2Y13 mediated responses. PPTN is a very potent antagonist at the P2Y14 receptor.

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“…We have read with great interest the article entitled ‟ Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor ” by Beavers et al, 1 published ahead of print in the Journal of Cardiovascular Pharmacology. We would like to thank the authors for this important summary of the evidence on this new drug but also express concerns that they have not properly interpreted the available data regarding its safety profile.…”

mentioning

confidence: 99%

Selatogrel and Other P2Y12 Inhibitors' Putative Off-Target Effects

Valgimigli

Storey

Sinnaeve

et al. 2022

Journal of Cardiovascular Pharmacology

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W e have read with great interest the article entitled "Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor" by Beavers et al, 1 published ahead of print in the Journal of Cardiovascular Pharmacology. We would like to thank the authors for this important summary of the evidence on this new drug but also express concerns that they have not properly interpreted the available data regarding its safety profile. The authors have wrongly deduced the phase 2 data generated in the context of patients with chronic 2 or acute coronary syndrome 3 , whereby no instances of ventricular pauses were actually observed. In particular, the authors stated that among patients with chronic coronary syndrome, common adverse events included dyspnea, dizziness, and ventricular pauses and went on to state that among patients with acute coronary syndrome, 14.9% of them suffered from ventricular pauses with selatogrel (n = 4 with 8 mg and n = 3 with 16 mg), including 2 patients, 1 in each arm, in which they were deemed treatment-emergent serious events. The figures reported by the authors actually refer to ventricular tachycardia, which is a relatively common complication of recent or ongoing myocardial ischemia and was deemed unrelated to the study drug by the investigators. No cases of ventricular pauses were recorded in either of these 2 studies. In addition, the assumption that the mechanism of ventricular pauses would be likely due to potential inhibition of adenosine reuptake is not supported by data from Baumann et al 4 2021, showing that selatogrel is a selective antagonist of the P2Y 12 receptor and does not interfere with adenosine uptake by human red blood cells in vitro at selatogrel concentrations of 10 mM. We disagree with the authors' suggestion that "it had been assumed that dyspnea with ticagrelor and cangrelor was due to the adenosine portions of the molecules" because this was never a widely supported assumption. It was certainly speculated that antagonism of ENT1 by ticagrelor was leading to increased extracellular adenosine levels and thus causing dyspnea, but the observation of similar rates of dyspnea with cangrelor and elinogrel undermined this assumption because these drugs do not antagonize ENT1 and the inactive metabolite of cangrelor is a much weaker ENT1 antagonist than ticagrelor. 5 With such differences in chemical structure between the reversibly binding P2Y 12 receptor antagonists, it seems unlikely that the "pyrimidine core" could have an effect on adenosine receptors that was independent of From the

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Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor

Cited by 7 publications

References 33 publications

Evolving Diagnostic and Management Advances in Coronary Heart Disease

Evolving Diagnostic and Management Advances in Coronary Heart Disease

Pharmacological characterization of P2Y receptor subtypes – an update

Selatogrel and Other P2Y12 Inhibitors' Putative Off-Target Effects

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