Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. (https://pubmed.ncbi.nlm.nih.gov/38720069/)

These scientists wanted to understand how a molecule called Lipoprotein(a) (Lp(a)) is formed in the body and how they can stop it from happening. Lp(a) is a particle that can increase the risk of heart problems. They found that Lp(a) is made when two other molecules, low-density lipoprotein (LDL) and apolipoprotein(a) (apo(a)), interact with each other and form a bond.

The scientists discovered that they can prevent this bond from forming by using small molecules that can interact with a specific part of the apo(a) molecule. They tested different compounds and found some that were very good at stopping the formation of Lp(a). They then made these compounds even stronger by changing their chemical structure and making them more powerful.

They gave these compounds to mice and monkeys and found that they could reduce the levels of Lp(a) in their bodies. They also made sure that these compounds did not affect another important molecule called plasminogen, which is needed for blood clotting.

Overall, the scientists found a promising compound called LY3473329 that could potentially be used as a medicine to lower Lp(a) levels in humans and reduce the risk of heart problems. This compound is currently being tested in clinical trials to see if it can help people stay healthy.

Diaz N., Perez C., Escribano AM., Sanz G., Priego J., Lafuente C., Barberis M., Calle L., Espinosa JF., Priest BT., Zhang HY., Nosie AK., Haas JV., Cannady E., Borel A., Schultze AE., Sauder JM., Hendle J., Weichert K., Nicholls SJ., Michael LF. Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. Nature. 2024 May;629(8013):945-950. doi: 10.1038/s41586-024-07387-z. Epub 2024 May 8.