Small-molecule IKKβ Activation Modulator (IKAM) Targets MAP3K1 and Inhibits Pancreatic Tumor Growth

Significance Pancreatic cancer is a deadly disease with limited therapeutic options. High expression of the kinase MAP3K1 is associated with poor survival among pancreatic cancer patients. MAP3K1 activates the kinase IKKβ, and our studies show that higher levels of activated IKKβ are found in patient-derived tumors as opposed to the surrounding normal tissue. We also show that inhibition of MAP3K1 by a drug-like compound 39-100 results in reduced levels of activated IKKβ. This leads to reduced tumor growth and reduced metastasis in pancreatic cancer models. Therefore, drug candidates like 39-100, that are IKKβ activation modulators, can be developed to treat pancreatic cancer.