Development of 6-amido-4-aminoisoindolyn-1,3-diones as p70S6K1 inhibitors and potential breast cancer therapeutics
In this study, we have identified a new class of compounds as p70S6K1 inhibitors that function as growth inhibitors of MCF7 breast cancer cells. The structural features imparting p70S6K1 inhibition potency to the compounds have been mapped. Our studies indicate that substitutions on the phenacetyl group residing in the cleft A of the protein do not contribute to the inhibition potency. Three compounds (<b>5b, 5d</b>, and <b>5f</b>) have been identified to have sub-micromolar inhibition potency for p70S6K1. These compounds also exhibited growth inhibition of MCF7 cells by 40%-60% in the presence of estradiol.
Authors
- Alison J. Thornton (ORCID: https://orcid.org/0000-0003-3689-4395)
- Jeanne C. Myers
- Jayalakshmi Sridhar (ORCID: https://orcid.org/0000-0002-4424-9874)
- Elijah Johnson-Henderson
- Kevin J. Petty
- Rajesh Komati (ORCID: https://orcid.org/0000-0002-9940-0690)
- Linh M. Tran (ORCID: https://orcid.org/0000-0001-8597-643X)
- Rion Sam
- Kim-Lea Reese (ORCID: https://orcid.org/0009-0007-3406-2671)
- Christopher J. Williams (ORCID: https://orcid.org/0000-0002-5808-8768)
- Hogyoung Kim (ORCID: https://orcid.org/0000-0002-1834-5133)
- V. Sridhar
Institutions
- Xavier University of Louisiana (US)
- University of New Orleans (US)
- Nicholls State University (US)
Publication Details
- Journal
- Frontiers in Molecular Biosciences
- Published
- 2024-12-19
- DOI
- https://doi.org/10.3389/fmolb.2024.1481912
- Primary Topic
- PI3K/AKT/mTOR signaling in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- Louisiana Cancer Research Consortium, Xavier University of Louisiana