OTUB2-IN-1 is a selective OTUB2 inhibitor with anti-tumor activity that inhibits the expression of PD-L1 protein in tumor cells and inhibits tumor growth, and can be used to study skin cancer and non-small cell lung cancer (NSCLC).

Incubation of recombinant GST-OTUB2 protein with OTUB2-IN-1 resulted in significant inhibition of Ub-R110 cleavage by GST-OTUB2 in a dose-dependent manner, suggesting that OTUB2-IN-1 can inhibit the hydrolytic activity of recombinant GST-OTUB2 protein toward its substrate Ub-R110 in vitro. [1]

Evaluated the therapeutic potential of OTUB2-IN-1 using a mouse LL/2 tumor model. OTUB2-IN-1 treatment significantly suppressed tumor growth and prolonged mouse survival, and no obvious toxicity was observed. To clarify the effect of OTUB2-IN-1 in tumor inhibition through regulation of PD-L1 in vivo, LL/2 cells with stably expressed PD-L1 and control plasmids were used to establish a tumor model. As expected, in comparison to the control group, overexpressed PD-L1 resulted in a substantial increase in tumor growth, whereas OTUB2-IN-1 significantly reduced the PD-L1-overexpressing tumor growth. [1]