Ciglitazone Explained

Ciglitazone (INN) is a thiazolidinedione. Developed by Takeda Pharmaceuticals in the early 1980s, it is considered the prototypical compound for the thiazolidinedione class.^{[1] [2] [3]}

Ciglitazone was never used as a medication, but it sparked interest in the effects of thiazolidinediones. Several analogues were later developed, some of which—such as pioglitazone and troglitazone—made it to the market.^[4]

Ciglitazone significantly decreases VEGF production by human granulosa cells in an in vitro study, and may potentially be used in ovarian hyperstimulation syndrome.^[5] Ciglitazone is a potent and selective PPARγ ligand. It binds to the PPARγ ligand-binding domain with an EC50 of 3.0 μM. Ciglitazone is active in vivo as an anti-hyperglycemic agent in the ob/ob murine model.^[6] Inhibits HUVEC differentiation and angiogenesis and also stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells.^[7]

Notes and References

1. Pershadsingh HA, Szollosi J, Benson S, Hyun WC, Feuerstein BG, Kurtz TW . Effects of ciglitazone on blood pressure and intracellular calcium metabolism . Hypertension . 21 . 6 Pt 2 . 1020–1023 . June 1993 . 8505086 . 10.1161/01.hyp.21.6.1020 . free .
2. Imoto H, Imamiya E, Momose Y, Sugiyama Y, Kimura H, Sohda T . Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives . Chemical & Pharmaceutical Bulletin . 50 . 10 . 1349–1357 . October 2002 . 12372861 . 10.1248/cpb.50.1349 . free .
3. Sohda T, Kawamatsu Y, Fujita T, Meguro K, Ikeda H . [Discovery and development of a new insulin sensitizing agent, pioglitazone] . ja . Yakugaku Zasshi . 122 . 11 . 909–918 . November 2002 . 12440149 . 10.1248/yakushi.122.909 . free .
4. Hulin B, McCarthy PA, Gibbs EM . The glitazone family of antidiabetic agents . Current Pharmaceutical Design . 2 . 85–102 . 1996 . 10.2174/1381612802666220920215821 . 252485570 .
5. Shah DK, Menon KM, Cabrera LM, Vahratian A, Kavoussi SK, Lebovic DI . Thiazolidinediones decrease vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells in vitro . Fertility and Sterility . 93 . 6 . 2042–2047 . April 2010 . 19342033 . 2847675 . 10.1016/j.fertnstert.2009.02.059 .
6. Willson TM, Cobb JE, Cowan DJ, Wiethe RW, Correa ID, Prakash SR, Beck KD, Moore LB, Kliewer SA, Lehmann JM . 6 . The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones . Journal of Medicinal Chemistry . 39 . 3 . 665–668 . February 1996 . 8576907 . 10.1021/jm950395a .
7. Xin X, Yang S, Kowalski J, Gerritsen ME . Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo . The Journal of Biological Chemistry . 274 . 13 . 9116–9121 . March 1999 . 10085162 . 10.1074/jbc.274.13.9116 . free .