Immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agents manifest improved survival in advanced hepatocellular carcinoma (HCC), but responses remain heterogeneous. Its high expression denotes an immunosuppressive TME. Targeting the NQO1/CXCL12/Tregs axis with Plerixafor may restore sensitivity and improve outcomes.

Overall, our study demonstrates that an NQO1-responsive prodrug strategy can effectively enhance the antitumor properties of dFdC. The optimized prodrug 2 warrants further development as a preclinical candidate drug.

In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD+/Ca2+ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

These findings suggest that compound 21 holds promise as a candidate for osteosarcoma treatment. Moreover, NQO1-targeting substrates present a promising pathway for the discovery of novel anti-osteosarcoma agents.

In conclusion, NQO1 may play a critical role in M2 polarization and accelerates HCC progression. The NRSHC model and accompanying tools offer valuable insights for personalized HCC treatment.

Importantly, the cell death induced by β-Lap and CGA in NQO1-overexpressing breast or lung cancers is closely linked to autophagy inhibition. These findings suggest that combining β-Lap and CGA might be a novel strategy for cancer therapy, particularly for overcoming drug resistance caused by autophagy induction in cancer cells.

The anti-proliferative activity evaluation revealed that most of these compounds exhibited superior inhibitory activity against MDA-MB-231 and MDA-MB-468 breast cancer cell lines compared to napabucasin...Meanwhile, 16c showed encouraging anti-tumor efficacy in the MDA-MB-231 xenograft model. In summary, this protocol provides a new vision and new chemical entity for dual targeting STAT3 and NQO1.

In vitro experiments demonstrated significant tumor-cell-specific activity of the cASO, while in vivo studies using an A549-Luc orthotopic lung tumor model revealed a substantial antitumor effect, primarily attributed to the suppression of survivin expression. This NQO1-activatable cASO represents a novel strategy for achieving tumor-cell-specific gene silencing and holds promise for the development of ASO prodrugs with enhanced therapeutic potentials.

LPS-induced iNOS production in RAW264.7 macrophages of the most promising agents discovered (5ab and 5ac) displayed concentration-dependent with comparable activities to the reference anti-inflammatory drug indomethacin. Molecular modeling studies (including QSAR, molecular docking and molecular dynamics) were accessed supporting the observed biological profiles.

Our findings suggest that NQO1 plays a crucial role in promoting migration and invasion in HPV16-positive cervical cancer cells, highlighting its potential as a therapeutic target.

Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

Notably, gene silencing experiments confirmed the critical roles of both NRF2 and AHR in mediating ATOIII-induced NQO1 expression. In conclusion, ATOIII exposure is found to upregulate the NQO1 enzyme through a transcriptional mechanism via AHR- and NRF2- dependent mechanisms, offering valuable insights into its therapeutic mechanisms.