In a new development, researchers at the University of Illinois have discovered a small molecule capable of influencing an immune process that plays a significant role in autoimmune diseases and cancers.
The researchers discovered the molecule, and enzyme inhibitor, after first examining how the immune system works and why some diseases can be resistant to treatments.
For the research, the team analyzed endoplasmic reticulum aminopeptidases 1 and 2, or ERAP1 and ERAP2, which are proteins accountable for over-trimming and trimming neoantigens and peptide antigens inside cells.
Excess trimming of neoantigens in tumors with ERAPs demonstrates chances lost to illuminate tumors, to be recognized and destructed by T-cells.
The modulation of ERAP2 and ERAP1 purpose with small molecule inhibitors provides an attractive method to dilute their over-trimming function, improve immune responses against tumors, and increase tumor visibility.
Meanwhile, in the study, the researchers describe the discovery of the first highly potent and selective small molecule inhibitors or ERAP2.
“This involved kinetic target-driven synthesis to find such inhibitors,” stated one of the research associates. Following this, X-ray crystallography was used to display the binding mode of the small molecules at the atomic level, which allowed for the improvement of the design for greater selectivity and potency.
Small molecules of ERAP2 could be used in association with other forms of cancer treatments, as well as the treatment of other diseases that are dependent on cell surface demonstration of antigens, such as infectious diseases as well as autoimmune diseases.
The research received support from grants from the National Institute of Health.