PMS-004 is an innovative polypeptide licensed by Primedicine Pharmaceutical from Canada Primary Peptides Inc. Its indication is myocardial infarction.

Its mechanism of action is as followed: When a myocardial infarction occurs, myocardial ischemia exposes cells to excitotoxicity and other stress conditions. It further leads to the binding of zD17 (Zinc finger DHHC containing 17) to JNK (c-Jun amino terminal protein kinase) (zD17 binds to JNK3 through its cytoplasmic domain CD1 and anchor domain D and E), and attracts mitogen-activated protein kinase 7 (MKK7) to form a compound. MKK7 further phosphorylates JNK through the action of its phosphorylated kinase. Then, the activated JNK causes cell death through two main pathways:

Firstly, after the activated JNK enters the nucleus, it acts on the downstream substrate c-Jun (a transcription regulator belonging to the leucine zipper family).JNK phosphorylates and activates c-Jun, which promotes the transcription of cell death genes and results in cell death. Secondly, the activated JNK activates caspase-3 and causes cell apoptosis through the mitochondrial apoptosis pathway. The research team has extracted and optimized the E-segment-specific amino sequence from zD17. The sequence is then fused it with the Tat amino acid sequence that promotes the transmembrane transport of the polypeptide, and subsequently transported the E-segment polypeptide into cells. The E-segment polypeptide competitively binds with JNK to prevent it from phosphorylation, thus further hindering the activation pathway of JNK to avoid the death of myocardial cells and plays a role in myocardial protection.

The project has completed the myocardial infarction pharmacodynamic model evaluation on rats, mice, and Bama pigs. PMS-004 plays a significant and obvious protection role in myocardial cells compared with the control group at the therapeutic dose by greatly reducing the injury area of myocardial infarction. It has shown a significant therapeutic effect and has ensured the feasibility of project implementation.

Link for related articles:

https://www.jneurosci.org/content/31/33/11980