Exploring target selectivity in designing and identifying PI3Kα inhibitors for triple negative breast cancer with fragment-based and bioisosteric replacement approach.

ABSTRACT: Triple-negative breast cancer (TNBC) is one of the most fatal malignancies in the world, accounting for 42% of all deaths due to metastasis. The significant development is hindered by the multi-drug resistance and poor patient compliance. PIK3CA gene mutation is one of the important causes of TNBC, which causes dysregulation of the cell cycle and cell proliferation. PI3Kα selective inhibition can decrease the TNBC by a significant level with minimal off-target effects. Novel compounds with high selectivity towards PI3Kα are crucial for treating TNBC. After extensive literature analysis, it was observed that fragment-based drug discovery, combined with structure-based virtual screening and bioisosteric replacement strategy, could provide a novel way for hit-to-lead optimization. The present

SUBMITTER: Halder D 

PROVIDER: S-EPMC11729857 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature