Tesaglitazar / AZ-242 CAS No. 251565-85-2

Product Description

Tesaglitazar, formally known as (2S)-2-ethoxy-3-[4-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]propionic acid, is a chiral propionic acid derivative centered at the C-2 center in the (S) configuration with an ethoxy substituent attached via an ether to a benzene ring bearing a 2-(4-methylsulfonyloxyphenyl)ethoxy tail; this structure provides a dual PPAR-α/γ agonist that is studied to simultaneously enhance fatty acid oxidation and insulin sensitivity for the treatment of type 2 diabetes and dyslipidemia. In the 12-week SIR trial, a dose-dependent dosing regimen of 0.1-1 mg once daily significantly improved triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein (LDL) volume in patients with abdominal obesity and insulin resistance by increasing concentrations of cardioprotective apolipoprotein A-I and reducing concentrations of atherogenic apolipoprotein B, apolipoprotein CIII, and low-density lipoprotein (LDL) particles. Despite these encouraging metabolic benefits, elevated creatinine and decreased glomerular filtration rate found in phase III clinical trials, as well as preclinical signals of fibrosarcoma formation and potential mitochondrial cardiotoxicity, led AstraZeneca to stop developing the drug in May 2006. Although teglitazar ultimately failed to enter the clinical stage, its potent apolipoprotein and lipid-modifying properties continue to provide guidance for the design of safer dual PPAR agonists to treat dyslipidemia caused by insulin resistance.

Send Us a inquiry!

Product Use & Characteristics

Basic physicochemical data

Molecular formula: C₂₀H₂₄O₇S

Molecular weight: 408.5 g mol⁻¹

IUPAC name: (2S)-2-ethoxy-3-[4-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]propanoic acid

Appearance: small-molecule, high-molecular-weight aromatic ether with a single chiral center (S-configuration at C-2), a methyl-sulfonyloxy tail and an ethoxy substituent on the propanoic-acid core.

Pharmacology & mechanism

Dual peroxisome proliferator-activated receptor (PPAR) agonist (PPAR-α ≈ PPAR-γ; slightly higher potency at γ).

Activates genes governing fatty-acid oxidation, adipocyte differentiation, insulin sensitivity and vascular anti-inflammatory pathways.

Uses (investigational)

Intended for type-2 diabetes mellitus and the atherogenic dyslipidemia of insulin-resistance syndrome.

Demonstrated dose-dependent improvements in fasting glucose, insulin resistance (HOMA-IR), triglycerides, HDL-C, apoA-I, apoB, apoCIII, LDL particle size and overall lipoprotein profile in non-diabetic obese subjects and in diabetic patients.

Explored as add-on to atorvastatin to correct residual dyslipidemia after statin therapy.

Clinical development & regulatory fate

Reached Phase III (GALLANT 6–9 and ARMOR studies).

Development discontinued May 2006 by AstraZeneca after external review concluded that elevations in serum creatinine and decreases in glomerular filtration rate outweighed expected benefits versus existing therapies.

Pharmacokinetics

Rapid oral absorption (Tmax ≈ 1 h) with essentially complete absolute bioavailability (~100 %), indicating negligible first-pass loss.

Plasma clearance 0.16 L h⁻¹; volume of distribution 9.1 L; elimination half-life ≈ 45 h.

>99.9 % plasma protein bound; blood-plasma partition 0.66.

Metabolised mainly to an acyl-glucuronide; ~20 % excreted unchanged in urine, >90 % of total radioactivity recovered in urine.

No detectable chiral inversion (S→R) in humans.

Pre-clinical safety/toxicology

Dose-related increases in serum creatinine and reduction in GFR in humans.

Fibrosarcoma formation in subcutaneous tissues of rats at high exposure.

GHS hazard statements: harmful if swallowed, irritant to skin, eyes and respiratory tract.

Possible mitochondrial cardiac toxicity and renal interstitial mesenchymal cell DNA synthesis observed in animals.

Non-clinical efficacy findings

In LDL-receptor knockout mice on a Western diet, tesaglitazar reduced atherosclerotic lesion area in females (independent of plasma lipid changes) and decreased adiposity in both sexes.

Analytical & synthetic notes

Quantitative LC–MS/MS assay in human plasma after 96-well solid-phase extraction; absolute recovery >95 %, LOQ 8.7 nM.

Stereospecific synthesis achieved via baker’s yeast-mediated asymmetric reduction of α-ethoxy-cinnamaldehyde precursors (>90 % ee) or enzymatic chiral resolution.

Why us!

Qingdao Sigma Chemical Co., Ltd., established in January 2017 and headquartered in Qingdao, China, is a reliable chemical supplier. Specializing in pharmaceuticals, biochemical intermediates, and research chemicals, the company offers a diverse product portfolio, including peptides (e.g., Tirzepatide, Semaglutide), nootropics, veterinary products, and APIs, often marketed with ≥99% purity and COA certification. We provides R&D, custom synthesis, and contract manufacturing services at various scales, while claiming a global export presence across 100+ countries. With international warehouses in the USA, Europe, Australia, and Canada, Qingdao Sigma Chemical also facilitates drop-shipping and reshipments, positioning itself as a key supplier for laboratory and research applications.