Tesaglitazar

Tesaglitazar is a dual-target PPARα/γ agonist with an EC₅₀ of 13.4 μM for rat PPARα and 3.6 μM for human PPARα. Tesaglitazar affects lipid and glucose metabolism by activating PPARα and PPARγ receptors, and has the potential to improve blood sugar and relieve pain. Tesaglitazar can be used to induce in vivo tumor models and can be used in the study of type 2 diabetes, dyslipidemia, and neuropathic pain^[1][2][3]. IC50 & Target:EC50: 13.4 μM (rat PPARα), 3.6 μM (human PPARα), 0.2 μM (PPARγ)^[1] In Vitro:Tesaglitazar mediates PPAR_α transcriptional activation with EC₅₀ of 13.4 μM and 3.6 μM for rat and human PPAR_α, respectively, and EC₅₀ of approximately 0.2 μM for rat and human PPAR_γ[1].
Tesaglitazar (2 μM; 6 hours pretreatment) significantly inhibited 10 μM Capsaicin (HY-10448)-induced cobalt influx into dorsal root ganglion (DRG) neurons in a cobalt uptake assay, and this inhibitory effect was PPAR_α- and PPAR_γ-dependent^[3].
In Vivo:Tesaglitazar (0.3-10 μmol/kg; po; once daily; 104 weeks) induces subcutaneous stromal sarcomas (fibrosarcomas) in Wistar Hannover Galas rats, and also induces a variety of non-neoplastic changes, such as cardiac hypertrophy and liver changes^[1].
Tesaglitazar (1, 10 μmol/kg; po; once daily; 2 or 12 weeks) in Wistar Hannover Galas rats, sustained stimulation of DNA synthesis, increased BrdU-labeled cells^[1].
Tesaglitazar (50 nmol/kg; sc; once daily; 14 days) reduced body weight, food intake, fasting blood glucose and insulin levels, improved insulin sensitivity and glucose metabolism, and had no significant effect on renal function in the male C57BL/6J diet-induced obesity (DIO) mouse model^[2].
Tesaglitazar (5 or 100 nmol/kg; sc; single dose) induced an acute deterioration in glucose tolerance at a high dose (100 nmol/kg), but a low dose (5 nmol/kg) reduced body weight, food intake and fasting blood glucose levels and improved glucose tolerance^[2] in the DIO mouse model^[2].
Tesaglitazar (10-20 μg/kg; intraperitoneal injection; single dose) significantly restored the mechanical paw withdrawal threshold (PWT) in the Streptozotocin (HY-13753)-induced diabetic neuropathy pain model in rats without affecting blood glucose levels^[3].