11-OXO-PROSTA-5Z,12E,14Z-TRIEN-1-OIC ACID

Description

CAY10410 is an analog of prostaglandin D₂/prostaglandin J₂ (PGD₂/PGJ₂) with structural modifications intended to give it PPARγ ligand activity and resistance to metabolism. 15-deoxy-Δ^12,14-PGJ₂ has been shown to be a potent ligand for PPARγ.¹ Metabolism of the cyclopentenone prostaglandins PGA₂, PGJ₂, and Δ¹²-PGJ₂ occurs via glutathione addition across the α,β unsaturated enone.² CAY10410 was designed as an analog of the PPARγ-binding prostaglandins which could not undergo this conjugation reaction. In human neuroblastoma SH-SY5Y cells, CAY10410 was not cytotoxic at up to 25 μM. It also failed to covalently modify thioredoxin or induce oxidative stress at 50 μM.³

References

1. Forman, B.M., Tontonoz, P., Chen, J., et al. 15-Deoxy-Δ^12,14-prostaglandin J₂ is a ligand for the adipocyte determination factor PPARγ Cell 83(5),803-812(1995).
2. Atsmon, J., Sweetman, B.J., Baertschi, S.W., et al. Formation of thiol conjugates of 9-deoxy-Δ⁹,Δ¹²(E)-prostaglandin D₂ and Δ¹²(E)-prostaglandin D₂ Biochemistry 29,3760-3765(1990).
3. Shibata, T., Yamada, T., Ishii, T., et al. Thioredoxin as a molecular target of cyclopentenone prostaglandins J. Biol. Chem. 278(28),26046-26054(2003).