picotamide (C-AM-01) / Curatis, CapiThera - LARVOL DELTA

Distinct Thromboxane A₂-Dependent Pathways Regulate Arachidonic Acid-Triggered VASP Phosphorylation at Ser239 and Ser157 in Human Platelets: Real-Time Visualization Reveals Superior Antithrombotic Efficacy by Targeting Thromboxane A₂ Signaling over Cyclooxygenase Inhibition. (PubMed, J Cell Physiol) - "Finally, picotamide demonstrated superior antithrombotic efficacy compared to aspirin at an equivalent dose, as evidenced by real-time intravital imaging of thrombotic platelet plug formation in vivo. These results highlight TXS inhibition as a promising strategy for modulating platelet activation and thrombosis."

Journal • Cardiovascular • Hematological Disorders • Myocardial Infarction • Thrombosis

Thromboxane synthase inhibitors: a new perspective in osteogenesis imperfecta. (HMGC 2026) - "Materials and We evaluated the safety and efficacy of picotamide and ozagrel, compared to alendronate and control, in wild-type (WT), Col1a2oim/+, and Col1a2oim/oim mice. The therapeutic repurposing of TXAS inhibitors could represent a promising new approach for the treatment of patients with osteogenesis imperfecta."

Genetic Disorders

Chymase - Independent vascular Ang 1-12/Ang II pathway and TXA generation are involved in endothelial dysfunction in the murine model of heart failure. (PubMed, Eur J Pharmacol) - "However, this response was inhibited by angiotensin I converting enzyme (ACE; perindopril), angiotensin II receptor type 1 (AT; losartan), and TXA receptor (TP; picotamide) antagonists in 12-month-old-Tgαq*44 mice only. In conclusion, the chymase-independent vascular Ang-(1-12)/Ang II pathway and subsequent TXA overactivity contribute to systemic endothelial dysfunction in the late stage of HF in Tgαq*44 mice. Therefore, the vascular TXA receptor represents a pharmacotherapeutic target to improve peripheral endothelial dysfunction in chronic HF."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • ANGPT1

CYCLOOXYGENASE-2 INHIBITION AS A NEW TOOL TO COMBAT ANGIOGENESIS INHIBITOR-INDUCED HYPERTENSION AND RENAL TOXICITY. (PubMed, J Hypertens) - "In conclusion, selective COX-2 inhibition combats angiogenesis inhibitor-induced hypertension and renal toxicity. SU paradoxically increases the PGI2/TXA2 ratio, particularly in the kidney. Although this upregulation might initially be protective, it could eventually contribute to renal toxicity, most likely because PGI2 exerts deleterious effects in excessive concentrations. Targeting excessive renal PGI2 production might be another promising strategy to prevent renal toxicity during angiogenesis inhibition."

Journal • Cardiovascular • Hypertension • Oncology • Renal Disease • EDN1

Synthesis, in vitro cytotoxicity and biological evaluation of twenty novel 1,3-benzenedisulfonyl piperazines as antiplatelet agents. (PubMed, Bioorg Med Chem) - "With adenosine diphosphate (ADP), arachidonic acid (AA) and collagen as inducers, respectively, the Born turbidimetric method was used to screen the antiplatelet activity in vitro of all target compounds at a concentration of 1.3 μM, with aspirin and picotamide as positive control drugs. Each of synthesized compounds in silico molecular property and ADME (absorption, distribution, metabolism and excretion) are predicted by using Molinspiration property engine v2018.10 and PreADMET online servers, respectively. Compared with other series of compounds in the previous stage, the two series compounds obtained after the introduction of piperazinyl have a similar in vitro activity."

Journal • Preclinical

Picotamide inhibits a wide spectrum of agonist-induced smooth muscle contractions in porcine renal interlobar and coronary arteries. (PubMed, Pharmacol Res Perspect) - "Picotamide inhibits a wide spectrum of vasoconstrictor-induced contractions in porcine interlobar and coronary arteries. Inhibition of vasocontraction may contribute to beneficial effects of picotamide in the cardiovascular system and kidney."

Journal • Preclinical • Cardiovascular • EDN1

Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis. (PubMed, Curr Vasc Pharmacol) - "This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk."

Journal • Retrospective data • Review • Cardiovascular • Peripheral Arterial Disease

Synthesis of 4-Methoxy-1, 3-Benzenediolylhydrazones and Evaluation of Their Anti-Platelet Aggregation Activity. (PubMed, Iran J Pharm Res) - "Results demonstrated that the activities of all compounds excelled the positive drug Picotamide (25.1% inhibition rate) and seven compounds (PNN01, PNN03, PNN05, PNN07, PNN09, PNN12, and PNN14) have efficiently inhibited platelet aggregation even higher than Clopidogrel (37.6% inhibition rate) induced by AA. Evaluation of cytotoxic activity of the compounds against L929 cell line revealed that none of the compounds have significant cytotoxicity. Thus, diolylhydrazones derives are potential to be antiplatelet aggregation inhibitors and maybe working in AA-induced selectively."

Journal

Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes. (PubMed, Curr Cardiol Rep) - "DECLARE DIABETES showed that adding cilostazol to dual antiplatelet therapy after a coronary stent procedure reduced rates of in-stent and in-segment late loss and increased rates of revascularization (p < 0.04). In PEGASUS-TIMI, daily ticagrelor demonstrated reduced rates of major adverse cardiovascular and cerebrovascular events (OR 0.84, p < 0.04). The DAVID trial compared daily picotamide with daily aspirin therapy, finding reduced mortality rates in the picotamide group (OR 0.55, p < 0.05). Lastly, ACUITY found bivalirudin monotherapy resulted in lower rates of major bleeding events when compared to a glycoprotein IIb/IIa inhibitor and heparin or bivalirudin combination regimen (p < 0.01)...Overall, it is wise to weigh the cardiovascular risk of a DM patient before prescribing antiplatelet medication. More research is necessary to determine a universal drug or combination of drugs that is safe and effective for DM patients."

Journal • Review