Cancer; inflammation

Mouse and cell culture studies identified a RIPK2-inhibiting analog of Iclusig ponatinib that could help treat colorectal cancer and asthma. In silico screening of Iclusig analogs for RIPK2 binding and in vitro testing of the top hit yielded a compound that inhibited RIPK2 activity with an IC₅₀ of approximately 8 nM. In two human colorectal cancer cell lines, the compound decreased proliferation compared with no treatment. In a mouse model of asthma, the compound decreased the total number of cells and the number of eosinophils in bronchoalveolar lavage fluid compared with vehicle. Next steps could include testing the compound in additional models of colorectal cancer and asthma.

Takeda Pharmaceutical Co. Ltd., Gruppo Angelini, Incyte Corp., Medison Pharma Ltd., Otsuka Pharmaceutical Co. Ltd. and Specialised Therapeutics Australia Pty. Ltd. market Iclusig, a pan-BCR-ABL tyrosine kinase inhibitor (TKI), to treat acute lymphoblastic leukemia (ALL). Takeda, Gruppo, Incyte and Otsuka market the compound to treat chronic myelogenous leukemia (CML). Takeda, Gruppo and Incyte have the compound in Phase II testing to treat acute myelogenous leukemia (AML). Takeda and Incyte have the compound in Phase II testing for various cancers...