Phytoestrogens and their synthetic analogues as substrate mimic inhibitors of CYP1B1 – An update (2020–2025)

Cytochrome P450 enzymes (CYPs) play crucial roles in metabolizing diverse substances, including drugs, pollutants, hormones, and steroids. Among them, CYP1B1 has gained significant attention due to its involvement in cancer initiation, progression, and drug resistance. Overexpression of CYP1B1 is frequently observed in multiple cancers, including breast, lung, colorectal, and brain cancers, making it an important therapeutic target. This review is an update covering the last six years (2019–2025) to our earlier publication proposing linker-based classification. Articles published over this period broadly covers efforts taken to increase the aqueous solubility $\alpha$-naphthoflavone derivatives and ability to reverse the resistance to main-stream anticancer agents. We also covered PET tracers and PROTACs designed to hit the CYP1B1 by conjugating appropriate elements to the potent CYP1B1 inhibitors reported earlier. Overall, this review highlights significant recent innovations and strategic advancements in CYP1B1 inhibitor research, offering promising directions for cancer diagnosis and treatment.