Oleoyl 3-carbacyclic Phosphatidic Acid

Cyclic Phosphatidic Acids (cPAs) are naturally occurring lysophosphatidic acid (LPA) analogs, characterized by a 5-membered ring formed between the sn-2 hydroxy group and the sn-3 phosphate. Carba-derivatives of cPA (ccPA) modify the sn-2 (2-ccPA) or sn-3 (3-ccPA) linkage, hindering the conversion of cPA into LPA. Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1) incorporates the 18:1 fatty acid oleate at the sn-1 position on the glycerol backbone, acting as a cyclic LPA analog. This compound, at a concentration of 25 μM, blocks MM1 cells' transcellular migration through mesothelial cell monolayers induced by fetal bovine serum (by 90.1%) or LPA (by 99.9%), without impeding cell proliferation. Additionally, 3-ccPA 18:1, in the 0.1-1.0 μM range, notably suppresses autotaxin, which plays a vital role in various cancer cell behaviors including survival, growth, migration, invasion, and metastasis.