Abstract
Receptor interacting protein kinase 2 (RIP2 or RICK herein referred to as RIPK2) is linked to the pathogen pathway that activates NFkB and autophagic activation. Using molecular modeling (docking) and chemoinformatics analyses we utilized the RIPK2/ponatinib crystal structure and searched in chemical databases for small molecules exerting binding interactions similar to those exerted by ponatinib. The identified RIPK2 inhibitors potently inhibited the proliferation of cancer cells by > 70% as well as inhibition of NFkB activity. More importantly, in vivo inhibition of intestinal and lung inflammation rodent models suggest effectiveness to resolve inflammation with low toxicity to the animals. Thus, our identified RIPK2 inhibitor may offer a possible therapeutic control of inflammation in diseases such as inflammatory bowel disease, asthma, cystic fibrosis, primary sclerosing cholangitis and pancreatitis.
- The American Society for Pharmacology and Experimental Therapeutics