Quantifying secondary pharmacology antagonistic drug effects on platelet function
The development of new drugs is often limited or even halted by their side effects on platelet function. In drug discovery, identifying compounds that might have secondary pharmacological effects on platelet function can contribute to de-risking and help with the progression of potential new drugs. Half-maximal inhibitory concentration (IC50 or pIC50 (-log10IC50)), the concentration of […]
Anti-platelet therapy: future directions
In our blog series on anti-platelet therapy, we have covered the development of both intravenous and oral therapies and the role of platelet function testing in the discovery, development and monitoring of these agents. In this latest commentary, we speculate on future directions in this area. The future landscape can be divided into two themes: […]
Platelet function testing – shifting applications
In the latest instalment of our antiplatelet therapy series, we take a look at platelet function testing and how requirements for it have shifted throughout the years. In our previous blogs, we have outlined the evolution of anti-platelet therapy and the pivotal role these therapies have come to play in the management of cardiovascular disease. […]
Intravenous antiplatelet therapy – for when the going gets tough
In the second instalment of our antiplatelet therapy series, we take a look at intravenous (IV) antiplatelet therapy and how it came to be used. In a previous blog1, we provided a brief overview of the 50-year evolution of oral anti-platelet therapy, which began with the findings of the first randomised, controlled trial of aspirin […]
The importance of platelet testing
While it is not a regulatory requirement to test the effect of all drugs on platelets, platelet testing can be an important stage of the drug discovery process that will help companies understand the possible effects of their compounds in development on platelets and de-risk further development process. The purpose of platelet testing There are […]
Oral antiplatelet therapy – half a century of evolution
It is now 50 years since the first randomised, controlled trial of aspirin in the secondary prevention of mortality from myocardial infarction (MI)[1]. Although the results of the trial were statistically inconclusive, positive signals were observed. Over the next two decades, multiple studies were conducted in a range of patient groups leading to the conclusion […]
Therapeutic antibodies can have an effect on platelet function
Monoclonal antibodies (mAbs) are being discovered and developed as new therapeutic approaches to combat different diseases such as cancers, autoimmune diseases, HIV and more. Some immunoglobulin G (IgG) mAbs have been shown to affect platelet function with risk of thrombotic or bleeding side effects occurring in patients. They can induce platelet activation by different mechanisms […]
Platelet Function Testing in Target Safety Assessment
Adverse findings in non-clinical safety/toxicity testing continue to be a major reason for failure and/or complexity in drug projects. Since primary target-related toxicity plays a role in a significant proportion of these failures, an in-depth assessment of potential adverse consequences of target modulation can provide an important de-risking step in the discovery phase. Target Safety […]
Platelet function testing in drug discovery projects: considerations and challenges
Unwanted effects of drug compounds on platelet function can include a risk of increased bleeding and thrombotic events, depending on whether inhibition or enhancement of platelet function is involved. Despite these risks, drug-induced platelet function problems do not always appear to be identified in the drug discovery & development process and are sometimes reported late, […]
Blog: Tyrosine kinase inhibitors can have an effect on platelet function
Tyrosine kinase inhibitors (TKIs) are widely used as a targeted strategy for cancer treatment. However, due to their broad kinase target spectrum, most TKIs inevitably have off-target effects. Platelet function has been shown to be inhibited by TKIs, as they rely on the activity of several tyrosine kinases, including Tec, Btk, SFK, Lyn, Fyn, Syk. […]
