Title: Synthesis of new derivatives of the lead S6K1 inhibitors as breast cancer therapeutics Authors: Rion Sam, Kymmia Petty, Rajesh Komati, Shahensha Shaik, Jayalakshmi Sridhar Abstract: Breast cancer (BC) is the second leading cause of death among woman in the United States. There are different types of breast cancers based off the receptors that are overexpressed. The typical receptors that are overexpressed are the estrogen receptor (ER+), the progesterone receptor (PR+), and the human epidermal growth factor receptor 2 (HER2). Triple positive breast cancer cells overexpress all of these receptors and triple negative breast cancer cells do not overexpress these three receptors. Triple negative breast cancer (TNBC) cells are harder to treat because there are no receptors for the chemotherapeutic drugs to act on. This is where the research in the Sridhar lab comes into play. My research deals with the design and synthesis of S6K1 inhibitors. Research has showed that the S6K1 kinase plays an important role in the proliferation, regulation, and invasion of triple negative breast cancer cells in patients. S6K1 is a ribosomal protein kinase that is a downstream target of mTOR in the PAM pathway. The inhibitors that have been synthesized in our lab show promising results with up to 86% of inhibition at 10 mM concentration. The S6K1 inhibitors exhibited growth inhibition of HER2+, ER+ and TN breast cancer cells. To produce these inhibitors a five-step reaction scheme is followed with the appropriate method of purification for each step. The grand scheme of the project is for the S6K1 inhibitors to function as potential breast cancer therapeutics, and to be a part of the push towards better results for chemotherapy and potentially towards a cure.

Synthesis of new derivatives of the lead S6K1 inhibitors as breast cancer therapeutics

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