elinogrel (PRT-060128) / Novartis, AstraZeneca - LARVOL DELTA

Platelet α-granule secretion fosters autoimmune neuroinflammation in an animal model of multiple sclerosis (ECTRIMS 2025) - "Importantly, pharmacological inhibition of platelet activation and degranulation using clinically approved antiplatelet agents such as acetylsalicylic acid or elinogrel attenuated EAE progression, underscoring its translational potential. Our findings demonstrate that soluble factors released from platelet α-granules contribute to CNS autoimmunity by promoting leukocyte infiltration, demyelination, and BBB disruption. Targeting platelet activation may thus offer a promising therapeutic strategy to modulate neuroinflammation in MS. Further studies are warranted to elucidate the underlying mechanisms linking platelet degranulation to immune-mediated CNS pathology."

Preclinical • Cardiovascular • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis

Inverse agonist efficacy of selatogrel blunts constitutive P2Y12 receptor signaling by inducing the inactive receptor conformation. (PubMed, Biochem Pharmacol) - "Specifically, using bioluminescence resonance energy transfer2 (BRET2) probes, selatogrel, ticagrelor, and elinogrel were shown to stabilize the inactive form of the Gi/o-G complex in cells with recombinant expression of the P2Y12 receptor. Selatogrel bound to pocket 1, spanning helix III to VII. Furthermore, the binding mode of selatogrel, suggesting steric overlap with the proposed binding site of ADP and the ADP analog 2-methylthioadenosine diphosphate (2MeSADP), agrees with the functional characterization of selatogrel preventing platelet activation by blocking ADP binding to the P2Y12 receptor."

Journal • Cardiovascular • Coronary Artery Disease • Hematological Disorders • Thrombosis

The potency of selatogrel, a reversible antagonist of the P2Y12 receptor, is affected by calcium concentration. (PubMed, Platelets) - "A comparable potency loss was also observed with the reversible P2Y12 receptor antagonists ticagrelor, cangrelor and elinogrel. In conclusion, our data suggest that in low calcium conditions (i.e., citrate-anticoagulated blood), there is a risk of underestimating the potency of reversible P2Y12 receptor antagonists. To avoid overdosing, and a potential increase in bleeding risk, we propose that the ex vivo evaluation of reversible P2Y12 receptor antagonists should be performed with platelet assay systems containing physiological calcium concentration."

Journal

[VIRTUAL] Method of Anticoagulation Influences Potency of Reversible P2Y12 Receptor Antagonists (ISTH 2020) - "Similar potency shifts were observed for the reversible P2Y12 antagonists ticagrelor, cangrelor and elinogrel. Selatogrel is a potent and reversible antagonist of P2Y12R. Radioligand binding experiments confirmed that selatogrel prevents ADP binding to P2Y12R. In functional platelet assays at low calcium concentration, the potency of selatogrel was reduced due to lower P2Y12R binding affinity and increased platelet response to ADP."

Acute Coronary Syndrome • Cardiovascular • F2

An update on novel antiplatelets in vascular patients. (PubMed, Curr Pharm Des) - "Vorapaxar remains the only novel antiplatelet that is approved for PAD. Other novel antiplatelets demonstrate positive results, but further studies focused on vascular patients are necessary. Novel experimental antiplatelets are still in early phases of the clinical and preclinical studies."

Clinical • Journal