Currently, more than 3.8 million women in the United States are diagnosed with breast cancer and it still remains one of the top leading causes of cancer-related death among women. The activity of ribosomal protein S6 kinase 1 (S6K1) correlates with breast cancer, as it is  based on the amplification of S6K1 localized chromosomal region 17q23 in 20% of primary breast cancers. S6K1 can be a conserved serine or threonine protein kinase, which serves as the principal kinase effector downstream of the PI3K/mTOR regulatory signaling pathway. Over-expression of S6K1 has been associated with cell transformation and elevated proliferation rates in tumors, poor prognosis, and an increased risk of local recurrence. S6K1 has also been found to play a major role in the progression of ER-positive (ER+) breast cancer, HER2-positive (HER2+) breast cancer, and node-negative premenopausal breast cancer. Inhibition of this kinase can prove to be beneficial for the treatment of several types of breast cancer. Our group has identified new molecules that are derivatives of 6-amido-4-aminoisoindoline-1,3-dione lead structure as S6K1 inhibitors with low micromolar inhibition potency (IC50 = 2-5 mM). These compounds also inhibited the growth of HER2+, ER+, and triple-negative breast cancer cells. We are presently standardizing the synthetic protocol for a new analog series 6-alkyl/arylamino-4-amino/halogenoisoindoline-1,3-dione that is derived from the lead compound. The main goal of our research is to address health disparities by designing derivatives of (S6K1) inhibitors to stop the growth of breast cancer. The synthetic sequence is detailed within this presentation.

Synthesizing derivatives of 6-amido-4-aminoisoindoline-1,3-dione lead compounds, to produce S6K1 inhibitors as potential preventatives of breast cancer

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.