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Description

S6K1 is an important protein kinase that is downstream to a variety of signaling pathways. S6K1 is a downstream target of mTOR (mammalian target of rapamycin), and relays signals to regulate several fundamental cellular and oncogenic processes including the enhancement of mRNA biogenesis, cap-dependent translation and elongation, and the translation of ribosomal proteins. In various cancers, S6K1 is shown to play a prominent role in cancer progression such as breast cancer, prostate cancer, non-small cell lung cancer (NSCLC), and brain tumors. For breast cancer, the hyperactivity of S6K1 has been suggested to be linked to the presentation of breast cancer in cell lines for estrogen positive breast cancer and HER2-positive breast cancer. Therefore, S6K1 overexpression may be closely related to the presentation of these two cancers and may be used as a therapeutic target for the suppression of S6K1 activity by inhibiting the activity of the protein. Our lab has identified 1,3-dioxoisoindolinyl monoamides as ATP-competitive inhibitors of the S6K1 protein. The derivatives of these compounds are synthesized in multistep synthesis in the lab and then tested against various cancer cell lines. The goal is to synthesize a compound that is a potent and selective inhibitor of S6K1 that can be used as cancer therapeutics.

Publication Date

2021

Keywords

Development, Inhibitors, Breast Cancer, Therapeutics

Disciplines

Biology | Chemistry | Life Sciences | Oncology | Organic Chemistry

Development of isoindoline-1,3-dione derivatives as S6K1 inhibitors to function as potential breast cancer therapeutics

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