Description
CAY10410 is an analog of prostaglandin D
2/prostaglandin J
2 (PGD
2/PGJ
2) with structural modifications intended to give it PPARγ ligand activity and resistance to metabolism. 15-
deoxy-
Δ
12,14-
PGJ
2 has been shown to be a potent ligand for PPARγ.
1 Metabolism of the cyclopentenone prostaglandins PGA
2, PGJ
2, and Δ
12-
PGJ
2 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-Δ12,14-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).
