Palmitoleoyl 3-carbacyclic Phosphatidic Acid

Cyclic phosphatidic acids (cPAs) are naturally occurring analogs of lysophosphatidic acid (LPA) in which the sn-2 hydroxy group forms a 5-membered ring with the sn-3 phosphate.^1,2 Carba-derivatives of cPA (ccPA) are modified at the sn-2 (2-ccPA) or sn-3 (3-ccPA) linkage, preventing the opening of cPA to produce lysophosphatidic acid (LPA).³ Palmitoleoyl 3-carbacyclic phosphatidic acid (3-ccPA 16:1) is a cyclic LPA analog that contains the 16:1 fatty acid, palmitoleate, at the sn-1 position of the glycerol backbone.³ At 25 μM, it inhibits the transcellular migration of MM1 cells across mesothelial cell monolayers in response to fetal bovine serum (86.9%) or LPA (99.9%) without affecting proliferation.³ 3-ccPA 16:1 significantly inhibits autotaxin (IC₅₀ = 620 nM),⁴ an enzyme that is important in cancer cell survival, growth, migration, invasion and metastasis. When delivered intraperitoneally, 3-ccPA 16:1 significantly reduces the number of lung metastases formed in mice injected with B16F10 melanoma cells in the tail vein.⁴