Telmisartan (BIBR 277) is an Angiotensin 2 Receptor Blocker. The mechanism of action of telmisartan is as an Angiotensin 2 Receptor Antagonist.

Ang II type 1 receptor:9.2 nM

In mice fed with a high-carbohydrate, high-fat diet, Telmisartan significantly reduced the accumulation of visceral fat and decreased the size of fat cells, surpassing the effects seen with valsartan. This reduction is associated with a significant decrease in liver triglyceride levels. Additionally, Telmisartan promoted an increase in calorie expenditure and prevented diet-induced weight gain.

Telmisartan acts as a selective partial agonist for PPARγ (EC50= 4.5 μM), achieving 25%-30% of the maximal activation effects seen with full agonists such as pioglitazone and rosiglitazone. In Hep3B cells, Telmisartan reduces both baseline and AGE-induced RAGE protein expression, and dose-dependently inhibits AGE-induced ROS production, subsequently inducing CRP gene and protein expression. It dose-dependently increases mRNA levels of PPARgamma target genes, such as AP2 and lipoprotein in adipocytes, both differentiating and fully differentiated. In differentiated adipocytes, Telmisartan decreases mRNA levels of type 1 11beta-hydroxysteroid dehydrogenase. It triggers adipogenic differentiation in 3T3-L1 cells and reduces ACC2 expression in mouse muscle myotubes to 60%-70%. Unlike candesartan (another ARB), Telmisartan dose-dependently downregulates RAGE mRNA levels, and effectively promotes the differentiation of 3T3-L1 preadipocytes.

Telmisartan is prepared as a 10 mM stock solution in DMSO. Cell proliferation is assayed using the CCK-8 cell counting kit. Briefly, 5×103 cells are seeded into each well of a 96-well plate and cultured in 100 μL of RPMI-1640 supplemented with 10% FBS. After 24 h, ARBs (telmisartan, irbesartan, losartan, and valsartan at 0, 1, 10, or 100 μM) or vehicle is added to each well, and cells are cultured for an additional 48 h. CCK-8 reagent (10 μL) is added to each well, and the plates are incubated at 37°C for 3 h. The absorbance is measured at 450 nm using a microplate reader.