thrombosis, as blood clots are called in medical jargon, can occur in veins or in arteries. Small thromboses often go unnoticed and resolve on their own. Larger clots, on the other hand, can lead to life-threatening heart attacks or strokes. Researchers now have a inhibitor as a new potential therapeutic agent to treatment identified by thrombosis.
The lipid kinase PI3KC2α is a potential pharmacological target for the treatment of thrombosis and potentially cancer. Scientists at the Leibniz Research Institute for Molecular Pharmacology (FMP) have now identified a potent inhibitor of their activity, which serves as the main structure for further drug development. The results of their study were published in the journal “Nature Chemistry Biology“published.
Blood thinners with serious side effects
As in a stream Message According to the FMP, thromboses such as venous thrombosis and pulmonary embolism, which occur in about one in 1,000 adults each year, pose a major threat to human health, especially in the elderly.
To combat blood clotting, patients take blood thinners, but they are heavy Side effects like bleeding (hemorrhage).
The lipid kinase PI3KC2α is known to have a significant influence on blood clotting, as it affects the function of the pads regulated, which are essential for triggering blood clotting, for example in response to increased blood pressure or atherosclerosis (hardening of the arteries).
Therefore, PI3KC2α is a suitable target for the development of new antithrombotic drugs. So far, however, no inhibitor described by PI3KC2α.
Optimized efficiency
Dr Wen Ting Lo of the working group of Prof. Volker Haucke is now working closely with the medicinal chemist Dr Marc Nazaré and his team, researchers from Toulouse and the FMP Screening Unit (led by Dr. Jens Peter von Kries) developed and characterized the first PI3KC2α inhibitors.
Following extensive chemical optimization studies, scientists succeeded in efficiency kinome-wide inhibitors, especially relative to all other lipid kinases.
One of these labeled compounds PITCOIN3 According to experts, it exhibits particularly marked selectivity for PI3KC2α and has been shown to impair platelet membrane remodeling and thrombus formation.
New possibilities for the treatment of thrombosis and cancer
“This breakthrough development was only possible based on our previous structural studies of PI3KC2α”says Dr. Lo, the study’s first author. Dr. Nazaré notes that the unexpected nonclassical binding mode of PITCOIN inhibitors offers a promising new concept for development related drug candidates shows.
PITCOIN could also be important tools to help other researchers, unknown functions of PI3KC2α to investigate and discover.
“The antithrombotic effect of PITCOIN inhibitors counteracts thrombosis via effects on the internal system membrane structure platelets and not by blocking their activation, opening an improved therapeutic window”according to Professor Haucke.
As stated in the press release, the presented results could open up new possibilities for the treatment of thrombosis and Cancer as evidenced by the property of PITCOINs to alter the migration of breast cancer cells in vitro. (ad)
Author and source information
This text corresponds to the requirements of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Sources:
Leibniz Research Institute for Molecular Pharmacology (FMP): Inhibitor of the lipid kinase PI3KC2α identified as a potential new therapeutic agent for the treatment of thrombosis, (accessed: September 18, 2022), Leibniz Research Institute for Molecular Pharmacology (FMP)
Lo WT, Belabed H, Kücükdisli M, Metag J, Roske Y, Prokofeva P, Ohashi Y, Horatschek A, Cirillo D, Krauss M, Schmied, C., Neuenschwander, M., von Kries, J., Médard, G. , Kuster, B., Perisic, O., Williams, RL, Daumke, O., Payrastre, B., Severin, S., Nazaré, M., Haucke, V.: Development of selective inhibitors of phosphatidylinositol 3- C2α kinase; in: Nature Chemical Biology, (published: 09/15/2022), Nature Chemistry Biology
Important Note: This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.
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