2-hydroxyflavanone

2-hydroxyflavanone (2HF) is a citrus-derived flavonoid that acts as a potent inhibitor of RLIP (RALBP1), an ATP-dependent efflux pump involved in the transport of glutathione-electrophile conjugates and the endocytosis of the epidermal growth factor receptor (EGFR). By inhibiting RLIP, 2HF downregulates the expression of key homologous recombination (HR) DNA repair genes, including BRCA1, BRCA2, and PALB2. This mechanism creates a transcriptomic environment similar to HR-deficient (HRD) mutated cells, effectively inducing a "BRCAness" phenotype. Consequently, 2HF has demonstrated the ability to sensitize BRCA-wildtype cancer cells, such as certain ER+ and triple-negative breast cancers, to the cytotoxic effects of PARP inhibitors. Preclinical studies suggest its utility in reducing spontaneous carcinogenesis and overcoming chemotherapy resistance in various malignancies.

Other names

2-hydroxy-2-phenyl-2,3-dihydrochromen-4-one2-hydroxy-2-phenyl-4-chromanone