Development of Novel STAT3 Inhibitors That Target Malignant Brain Tumors
Signal transducer and activator of transcription 3 (STAT3) proteins are transcription factors driving cancer initiation, proliferation and immunosuppression. Mounting evidence suggests that STAT3 plays a key role in malignant brain tumors; therefore, the STAT3 pathway is an attractive therapeutic target.
Effective new therapies are needed to alleviate the suffering and improve the prognosis facing people with these central nervous system tumors. The Experimental Drug and Therapeutics for Pediatric Brain Tumor Laboratory at Mayo Clinic has successfully developed a series of novel drugs and found them to be potent inhibitors of the STAT3 pathway. Currently Dr. Daniels and his research team are improving and refining the in vitro potency and selectivity of these pyrazole-based STAT3 inhibitors to determine the in vivo efficacy of these inhibitors in malignant murine brain tumor models. The goal is to identify a lead compound that is cost-effective to synthesize, potent and selective to the STAT3 signaling pathway. The results will directly lead to preclinical drug studies, including safety and pharmacokinetic optimization.