The present invention contemplates new members of the diprovocim family of compounds that exhibit improvements in both
potency and
efficacy in the murine
system, permitting more effective use
in vivo in animal models while maintaining the remarkable activity
agonist towards human TLR1 / TLR2. The prototypical new
agonist called diprovocim-X exhibits the same excellent
potency and
efficacy of diprovocim-1 in human THP-1 cells (EC50 of 140 pM vs 110 pM with
efficacy 100% that of diprovocim-1 and Pam3CSK4), and displays a superb EC50 of 750 pM in mouse macrophages with an efficacy 550% that of diprovocim-1. Diprovocim-X served as an
adjuvant in vivo in mice when co-administrated with a non-immunogenic
antigen (OVA), indicating stimulation of the adaptive immune response. These the new diprovocim family compounds are now functionalized for linkage to antigenic, targeting, or delivery moieties, properties to enable precision activation of coordinated innate and adaptive immune responses in target tissues.