ALPK1 agonist PTT-936

An orally bioavailable innate immune agonist and activator of the cytosolic alpha-protein kinase 1 (ALPK1) that is an ADP-heptose derived from bacteria, with potential immunomodulating and antineoplastic activities. Upon oral administration, ALPK1 agonist PTT-936, being a ADP-heptose, specifically targets and binds to ALPK1, thereby activating the ALPK1-mediated signal transduction pathway. This initiates the phosphorylation of TRAF-interacting protein with forkhead-associated domain (TIFA), leading to the activation of pro-inflammatory nuclear factor kappa-B (NF-kB) signaling, cytokine induction and the activation and recruitment of immune cells, such as natural killer (NK) cells and T cells. This leads to tumor cell eradication and inhibits tumor cell proliferation. ALPK1, a bacterial pattern recognition receptor (PPR), is involved in bacterial pathogen recognition and plays a key role in innate immune defenses against bacterial infection. It recognizes ADP-heptose, a metabolite released during the biosynthesis and degradation of lipopolysaccharides (LPS), which is present in bacteria but not present in mammalian cells.