PPAR-γ Ligand R&D for IBD

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependently transcriptional regulators of a family of nuclear hormone receptor superfamily with important roles in target gene regulation, in energy production, lipid metabolism and inflammation. PPAR-γ as a PPAR subtype is specifically highly expressed in the enterocytes, which confers key roles in the regulation of inflammation. Recent evidence from basic research and patient studies further documenting PPAR-γ as the major functional receptor mediating the common aminosalicylate activities in the prevention and treatments for inflammatory bowel disease (IBD). Based on advances in our basic understanding of disease mechanisms and discoveries of numerous new experimental compounds with PPAR activity, development of IBD drugs based on PPAR activity is becoming a promising approach.

Fig. 1. Expression and molecular mechanisms of PPARs in IBD. (Decara, et al., 2020)

Our PPAR-γ Ligand R&D Services

The Ace Therapeutics team is poised to add significant value to your efforts in PPAR-γ ligand discovery, optimization and characterization through in vitro and in vivo preclinical evaluation. Ace Therapeutics' strengths include a number of experts with deep knowledge of the possible role of PPAR-γ in IBD pathophysiology and insights that will aid you in the development of successful therapeutic strategies targeting the PPAR-γ receptor.

We integrate multidisciplinary approaches from medicinal chemistry, molecular biology and pharmacology to help our clients rationally optimize or create novel PPAR-γ agonists with topical effect and selective targeting of the colon.

Synthesis and Optimization of PPAR-γ Ligands

• We use molecular modelling computer programs to do virtual screening for the identification of candidate molecules capable of binding to PPAR-γ, taking into account molecular shape, polarity, hydrogen bond donor and acceptor characteristics, among others.
• We alter the structure of existing PPAR-γ ligands to increase their hydrophilicity or increase their potency.
• We use the strategy of computer simulations to predict the binding modes of small molecules to PPAR-γ and optimise their contacts by docking analysis, in the hope of activating this molecule in intestinal epithelial cells.

Preclinical Study of PPAR-γ Ligands

• As for PPAR-γ activity, PPAR-γ activity assays are conducted on cell lines such as the colon cancer cell lines Caco-2 and HT-29 to determine the agonist activity of the compound.
• Additional studies are conducted in animals with cell type-specific expression of PPAR-γ to identify the primary cellular source responsible for the therapeutic effects of PPAR-γ.
• Our animal models of colitis support the study of the key role of PPAR-γ activation in the regulation of inflammation and immune responses.
• We assist customers in analyzing the close links between intestinal‐microbial interactions and regulation of PPAR-γ expression by epithelial cells of the colon.
• Development of IBD therapeutic strategies seeks drug combinations with additive or synergistic properties through PPARs/RXR heterodimers.

Ace Therapeutics is dedicated to helping pharmaceutical companies develop and test PPAR-γ activators that control the inflammation and better handle of host-bacterial interactions. We provide reliable preclinical data on the anti-inflammatory effects of PPAR-γ in experimental models of IBD. If you are interested in our services, please do not hesitate to contact us.