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HomeScienceCompound effectively targets blood clots without elevating bleeding risk.

Compound effectively targets blood clots without elevating bleeding risk.

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Schematic representation of a general polyP-linked polyimolecular inhibitor (MPI). Aggregate charges on a polyP, changes in the electronic microstate of MPI induce a change in the protonability of MPIamine amines, resulting in a tunable proton state capable of recruiting protons to successfully bind polyP. The recruitment of protons upon MPI-polyP binding was demonstrated using calibrated thermogravimetric measurements. c Structure of hyperbranched polyglycerol (HPG), a polymer core in MPI. Dr Polyethylene glycol (PEG) brush structure on MPI. H Structures of the cationic binding groups CBG I and CBG II conjugated on the surface of HPG-PEG for polyP binding. The pKa The values ​​of the amino nitrogen atoms in CBG I attached to HPG-PEG are 8.4, 7.0 and 3.7 and on CBG II attached to HPG-PEG are 8.9, 6.5 and 3.6 based on titration potential. credit: Nature Communications (2023). DOI: 10.1038/s41467-023-37709-0

Safer and more effective blood thinners could be on the way after a groundbreaking discovery by researchers at the University of British Columbia and the University of Michigan, published today in Nature Communications.

By combining their expertise in blood clotting systems and chemical composition, the researchers designed a new compound called MPI 8 that offers the potential to prevent blood clots without any increased risk of bleeding – a common side effect of existing blood thinners.

“The development of MPI 8 represents a significant advance in the field of blood clot prevention and treatment,” said Dr. “By targeting a specific molecule involved in clot formation without disrupting the normal clotting process, we have created a blood thinner that has proven to be safer and more effective in animal models, with huge potential to improve human life as well.”

More research will be needed to confirm the safety and efficacy of MPI 8 in humans, but the initial results provide hope for a new era in blood clot prevention and thrombolytic therapy while serving as evidence of the power of research medicine collaboration.

Blood clots are a serious health concern affecting millions of people around the world. When left untreated, it can lead to life-threatening conditions such as deep vein thrombosis, heart attack, pulmonary embolism, and stroke.

Blood thinners, also known as anticoagulants or anticoagulant medications, are essential in treating and preventing blood clots, but they carry significant bleeding risks. This can cause complications and limit their use in some patients.

Existing blood thinners such as heparin, direct oral anticoagulants (DOACs), and warfarin work by targeting enzymes necessary for blood clotting. However, they must be dosed and carefully monitored because inactivation of those enzymes compromises the normal clotting process needed for wound healing.

The University of British Columbia and Michigan researchers took an innovative approach to target polyphosphate instead, a molecule involved in blood clotting that speeds up the process but is not essential to it.

“Our thinking was that polyphosphates might be a safer target to chase with an anticoagulant drug, because it would only slow these clotting reactions — even if we removed 100 percent of the polyphosphate’s action,” said Dr. Jim Morrissey, professor of chemistry. biology and internal medicine at the University of Michigan whose work has highlighted the role of polyphosphates in blood clotting.

“We really had to come up with a very new way to target it compared to the usual drugs that target clotting, and this is where Dr. Kezakidathu’s lab expertise became very important.”

After building a library of potential molecules and screening them for desired criteria, Kizhakkedathu’s lab focused on MPI 8. This unique molecule has “smart” binding groups with positive charges that are attracted to the negative charge of the polyphosphate. It will bind to polyphosphates and block them while leaving cells and other negative proteins in the body alone, eliminating toxic side effects.

In preclinical studies, MPI 8 showed remarkable efficacy in preventing blood clots in mice without increasing the risk of bleeding. The drug showed no signs of toxicity, even at higher doses.

“Not only is the drug showing promise as a safer and more effective option for patients, but the design platform we used to create MPI 8 is flexible, which may allow the development of additional compounds with similar properties and efficacy,” said Dr. Chanel. La, who worked on the project with a Ph.D. in chemistry. Student at Kizhakkedathu Laboratory.

“Assuming our work continues to produce positive results, I would be very excited to get MPI 8 into an approved clinical trial and bring this drug closer to reality for patients in need.”

more information:
Smart anticoagulants without bleeding side effects through chargeable tunable ligand design, Nature Communications (2023). DOI: 10.1038/s41467-023-37709-0

Provided by the University of British Columbia


the quote: New compound targets blood clots without increasing bleeding risk (2023, April 26) Retrieved April 26, 2023 from https://phys.org/news/2023-04-compound-blood-clots.html

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