P2Y12 antagonists: Approved drugs, potential naturally isolated and synthesised compounds, and related in-silico studies

An Overview of Marketed Nucleoside and Nucleotide Analogs

“…Bottlenecks include, inter alia , the lack of selectivity among the various P2Y receptors, the highly polar nature of the ligands rendering them not orally bioavailable, and the metabolic lability of many of the ligands. An exception is the P2Y12 receptor, for which two antagonists are marketed (Al‐Najjar, Saqallah, Abbas, Al‐Hijazeen, & Sibai, 2021). Cangrelor is used to reduce platelet aggregation by intravenous application.…”

Dual Antiplatelet Therapy: Guidance for Nurse Practitioners

“…7,8 P2Y 1 and P2Y 12 are G-protein coupled receptors which, when activated, cause morphological changes in platelets and stabilization of the thrombus. 9 Rationale and Recommendations for DAPT DAPT comprises 2 antiplatelet agents with different mechanisms of action: aspirin and a P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor). Aspirin irreversibly and selectively inhibits the platelet enzymes cyclooxygenase 1 (COX-1; involved in platelet production of thromboxanes) and COX-2 (affects upregulation of prostaglandins with vasodilator and antiaggregation activity).…”

“…10 The P2Y 12 inhibitors clopidogrel and prasugrel are thienopyridine prodrugs that require enzymatic conversion to their active metabolites, which irreversibly bind to P2Y 12 receptors, thereby inhibiting the platelet activation-aggregation cascade triggered by ADP. 9 Activation of clopidogrel is largely dependent on cytochrome P450 2C19 (CYP2C19). 9 Unlike thienopyridines, ticagrelor is a cyclopentyl-triazolopyrimidine with distinct pharmacokinetic and pharmacodynamic properties.…”

“…9 Activation of clopidogrel is largely dependent on cytochrome P450 2C19 (CYP2C19). 9 Unlike thienopyridines, ticagrelor is a cyclopentyl-triazolopyrimidine with distinct pharmacokinetic and pharmacodynamic properties. Ticagrelor is active upon administration, has a rapid onset of action, and reversibly and noncompetitively binds to the P2Y 12 receptor, thereby providing continued inhibition, even of new platelets.…”

QSAR, structure-based pharmacophore modelling and biological evaluation of novel platelet ADP receptor (P2Y12) antagonist

“…[12][13][14] A thorough review of the approved drugs, potential naturally isolated and synthesised compounds, and related in silico studies has been made recently by our team. 5 Designing pharmacophore models regarding the structural features of the target protein is commonly called structure-based pharmacophore modelling. The potential interactions of the co-crystallized ligand in proteins will be investigated using this approach.…”