RT Journal Article
SR Electronic
T1 Identification and Characterization of Novel Receptor Interacting Serine/threonine‐Protein Kinase 2 (RIPK2) Inhibitors Using Structural Similarity Analysis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.117.247163
DO 10.1124/jpet.117.247163
A1 Mohamed Salla
A1 Rodrigo Aguayo-Ortiz
A1 Danmaliki Gaddafi Ibrahim
A1 Alaa Zare
A1 Ahmed Said
A1 Jack Moore
A1 Vrajeshkumar Pandya
A1 Robin Manaloor
A1 Sunny Fong
A1 Anna R Blankstein
A1 Spencer Gibson
A1 Laura Ramos Garcia
A1 Pascal Meier
A1 Khushwant S. Bhullar
A1 Basil P. Hubbard
A1 Yahya Fiteh
A1 Harissios Vliagoftis
A1 Ing Swie Goping
A1 Dion Brocks
A1 Peter Hwang
A1 Jose Carlos A Martinez Velazquez
A1 shairaz baksh
YR 2018
UL http://jpet.aspetjournals.org/content/early/2018/03/19/jpet.117.247163.abstract
AB 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.