Claudin 1 (CLDN1), a membrane tight junction protein, is often overexpressed in multiple solid tumors including breast, colon, stomach, and liver 1-4 .Nonjunctional CLDN1 has been shown to promote exclusion of T cells and resistance to checkpoint inhibition, which could be reversed upon targeting of CLDN1 using monoclonal antibodies5 . Transpiring from these results, this project aimed to use Optim.AI® to identify effective optimal drug combinations that include a CLDN1 inhibitor (CLDN1i) against colorectal cancer (CRC).