Ciglitazone

Ciglitazone

Ciglitazone (INN) belongs to the thiazolidinedione class of compounds. Originally developed by Takeda Pharmaceuticals during the early 1980s, ciglitazone stands as the prototypical molecule for this category, laying foundational knowledge and interest in the broader field of thiazolidinediones.

Background

While ciglitazone itself was never commercialized as a therapeutic drug, its discovery prompted research into the pharmacological potential of thiazolidinediones. This subsequently led to the development of several analogues, with notable ones like pioglitazone and troglitazone eventually being introduced to the pharmaceutical market.

Pharmacological Properties

Ciglitazone's mechanisms and effects can be categorized as follows:

• PPARγ Ligand Activity: Ciglitazone functions as a potent and selective PPARγ (Peroxisome Proliferator-Activated Receptor gamma) ligand. It demonstrates an affinity for the PPARγ ligand-binding domain, with an EC50 value of 3.0 µM.
• Anti-hyperglycemic Agent: Ciglitazone exhibits in vivo anti-hyperglycemic properties, as evidenced by its efficacy in the ob/ob murine model, a common mouse model for studying diabetes.
• VEGF Production and Ovarian Hyperstimulation Syndrome (OHSS): In vitro studies using human granulosa cells revealed that ciglitazone significantly reduces VEGF (Vascular Endothelial Growth Factor) production. Due to this property, it has potential therapeutic applications in conditions like ovarian hyperstimulation syndrome (OHSS), although further research is needed.
• Effects on Differentiation and Angiogenesis: The compound inhibits HUVEC (Human Umbilical Vein Endothelial Cells) differentiation and angiogenesis, which are processes linked to vascular development and wound healing.
• Impact on Stem Cells: Ciglitazone has shown the ability to promote adipogenesis (fat cell formation) and suppress osteoblastogenesis (bone cell formation) in human mesenchymal stem cells. This sheds light on its potential influence on tissue regeneration and healing.

Legacy

Though ciglitazone itself never became a medication, its discovery and the subsequent insights gathered played a pivotal role in expanding the realm of diabetes management, leading to the creation and commercialization of effective thiazolidinedione drugs. Furthermore, the compound's diverse pharmacological properties continue to inspire research into various therapeutic applications, ranging from metabolic disorders to reproductive health.

References

• Takeda Pharmaceuticals. History of Thiazolidinediones.
• In vitro studies on human granulosa cells and Ciglitazone.
• PPARγ ligand-binding studies and Ciglitazone.
• Efficacy of Ciglitazone in the ob/ob murine model.