Toll-like receptor (TLR) 4 is a subtype of TLRs, a major family of pattern recognition receptors (PRRs) expressed on various cells that recognize pathogen-specific components of microbial invaders. TLR4 and its accessory molecule MD-2 form a stable TLR4-MD-2 receptor complex when activated with an appropriate ligand triggering an initial innate immune response that protects the host against a broad spectrum of unrelated pathogens, in addition to stimulating enhanced antigen-specific innate immunity.<br/><br/>This talk will describe the development of a novel series of TLR4 agonists, the Diamino Allose Phosphates (DAPs), demonstrating remarkable stability in aqueous formulations. The DAP ligands are capable of eliciting robust TLR4 mediated innate and adaptive immune responses in multiple immunotherapeutic applications. This new class of TLR4 agonists encompasses a non-hydrolyzable 3-amide bond instead of the classical 3-ester bond present in natural and synthetic Lipid A derivatives. This DAP series is more potent than the known TLR4 agonists' benchmarks MPLA and GLA and demonstrates equivalent or improved TLR4 activity to other known synthetic TLR4 agonists CRX-524 and CRX-601. The new compounds are finding promise as adjuvants and monotherapy with a lead DAP expected to enter phase 1 clinical trial in 2023 to treat allergic rhinitis.

Development of diamino allose phosphates (DAPs): A novel series of toll-like receptor 4 agonists, promising vaccine adjuvants and immunotherapeutics

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.