Development of Drugs Targeting Toll-like Receptors in IBD

Toll-like receptors (TLRs) are a class of proteins that play an important role in the innate immune system and are involved in inflammatory processes. As the major important pathogen pattern recognition molecules (PPRs), TLRs recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In the intestine, TLR-dependent NF-κB activation plays a crucial role in maintaining epithelial homeostasis and regulating infection and inflammation, and dysregulated TLR signaling has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Therefore, modulation of TLRs represents an innovative immunotherapeutics for the treatment of IBD.

Fig. 1. Role of toll-like receptors in inflammatory bowel disease. (Kordjazy, et al., 2018)

Our TLR Agonist and Antagonist R&D Services

Ace Therapeutics is staffed with excellent scientists with years of experience in fields such as immunology, medicinal chemistry and pharmacology. Through our in-depth knowledge of innate immune-mediated regulation of intestinal pathophysiology, we will help clients develop novel drugs for TLRs such as antagonists of TLR-signaling and agonists of their negative regulators.

Types of Drugs Targeting Toll-like Receptors That We Can Develop

We use a variety of approaches, including ligand mimetics to activate TLRs and antibodies or small molecules to inhibit them, to discover therapeutics that enhance or blunt TLR activity. Our drug development follows a traditional phase-by-phase approach wherein each phase must provide data without confounders to justify moving on to the next phase of research.

Synthesis and Optimization of TLR Agonists and Antagonists

• We provide the fundamental basis for the medicinal chemistry behind the rational design of TLR agonist/antagonists for the treatment of IBD, which is kindled by our elucidation of the structural basis for several TLRs (TLR1, TLR2, TLR4, TLR5, TLR6, TLR3, TLR7, TLR8 and TLR9)
• Using such novel screening techniques and high-throughput analysis, we identify potent modulators of TLR signalling that will either promote or attenuate signaling.
• We can then feasibly anticipate the biological activity of the designed molecules as well as optimize their properties for pharmacokinetics with the help of molecular biology, biochemistry and computational modelling.

Preclinical Evaluation of TLR Agonists and Antagonists

We offer several in vitro inflammation models and colitis animal models to support the preclinical testing of TLR agonists and antagonists. Our objective is to assist in deciphering the underlying mechanisms, efficacy and safety of the therapeutic agents.

• Study of mechanism. Deeper analysis of the mechanism of action of TLR-targeting and some components of the signalling pathway drugs in IBD.
• We also can carry out pharmacodynamics studies to investigate the efficacy of intestinal TLR agonists and antagonists in treating intestinal inflammation alongside intestinal inflammation scores, pathomorphology of the intestinal histopathology and expression levels of the relevant inflammatory markers.
• Toxicology studies. We evaluate the safety of TLR agonists and antagonists in standard toxicology studies.

At Ace Therapeutics, we offer comprehensive services to help clients analyze the potential mechanisms of the TLR signaling pathway in IBD. Also, our team provides the latest potential therapeutics for IBD, ranging from customized solutions to your specific need.Get in touch with us, and we will provide you with relevant information on our services.