Identification of a RAD52 Inhibitor Inducing Synthetic Lethality in BRCA2-Deficient Cancer Cells
The breast cancer susceptibility gene 1/2 (BRCA1/2) is frequently mutated in many malignant tumors, such as breast cancer and ovarian cancer. Studies have demonstrated that inhibition of RAD52 gene function in BRCA2-deficient cancer causes synthetic lethality, suggesting a potential application of R...
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| Main Authors: | , , , |
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| Format: | Book |
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Frontiers Media S.A.,
2021-04-01T00:00:00Z.
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| Summary: | The breast cancer susceptibility gene 1/2 (BRCA1/2) is frequently mutated in many malignant tumors, such as breast cancer and ovarian cancer. Studies have demonstrated that inhibition of RAD52 gene function in BRCA2-deficient cancer causes synthetic lethality, suggesting a potential application of RAD52 in cancer-targeted therapy. In this study, we have performed a virtual screening by targeting the self-association domain (residues 85-159) of RAD52 with a library of 66,608 compounds and found one compound, C791-0064, that specifically inhibited the proliferation of BRCA2-deficient cancer cells. Our biochemical and cell-based experimental data suggested that C791-0064 specifically bound to RAD52 and disrupted the single-strand annealing activity of RAD52. Taken together, C791-0064 is a promising leading compound worthy of further exploitation in the context of BRCA-deficient targeted cancer therapy. |
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| Item Description: | 1663-9812 10.3389/fphar.2021.637825 |