T-0901317

T-0901317 is a synthetic compound that acts as a selective agonist for the Liver X Receptor (LXR), a type of nuclear receptor involved in the regulation of cholesterol, fatty acid, and glucose homeostasis. This compound has been studied for its potential therapeutic applications in treating conditions such as atherosclerosis, diabetes, and neurodegenerative diseases.

Chemical Structure and Properties

T-0901317 is a non-steroidal compound with the chemical formula C29H41NO3. It is characterized by its ability to bind to and activate both LXRα and LXRβ subtypes, which are expressed in various tissues including the liver, intestine, adipose tissue, and macrophages.

Mechanism of Action

T-0901317 functions by binding to the ligand-binding domain of LXRs, inducing a conformational change that promotes the recruitment of coactivators. This activation leads to the transcription of target genes involved in lipid metabolism, such as ABCA1, SREBP-1c, and FAS. These genes play crucial roles in cholesterol efflux, fatty acid synthesis, and lipogenesis.

Pharmacological Effects

The activation of LXRs by T-0901317 has been shown to:

• Increase cholesterol efflux from macrophages, reducing foam cell formation and potentially slowing the progression of atherosclerosis.
• Enhance hepatic lipogenesis, which can lead to increased triglyceride levels, a potential side effect that limits its therapeutic use.
• Modulate glucose metabolism, improving insulin sensitivity in some models of diabetes.
• Influence inflammatory pathways, which may have implications for neurodegenerative diseases.

Research and Clinical Implications

While T-0901317 has demonstrated promising effects in preclinical studies, its use in clinical settings is limited due to its side effects, particularly the induction of hypertriglyceridemia. Research continues to focus on developing more selective LXR agonists that retain the beneficial effects on cholesterol metabolism without adverse lipid accumulation.

Safety and Side Effects

The primary concern with T-0901317 is its effect on lipid metabolism, particularly the increase in triglyceride levels. This side effect poses a risk for the development of hepatic steatosis and other metabolic disorders. Therefore, careful consideration and monitoring are required when using LXR agonists in therapeutic contexts.

Also see

• Liver X Receptor
• Cholesterol metabolism
• Atherosclerosis
• Diabetes
• Neurodegenerative diseases