To explore this, we conducted a drug repurposing screen and identified three HIF1α inhibitors (bakuchiol, BAY-87-2243, 2-methoxyestradiol) whose sensitivities were correlated with sensitivity to Deltarasin, a KRAS inhibitor. Our findings suggest that HIF1α inhibitors could be used to sensitize PDAC to radiotherapy and KRAS inhibitors.

Conclusively, 2ME ameliorates ACN-induced gastric injury. This protective effect may be associated with the antioxidant, anti-inflammatory, and anti-apoptotic properties of 2ME, in addition to a potential modulation of the TLR4/MYD88/phospho-p38 MAPK signaling pathway.

This study revealed a novel mechanism in which BMAL1 downregulation under aging and HFD conditions promotes NASH progression by binding to HIF-1α and modulating the glycolysis-NLRP3 inflammasome axis.

A USP13 inhibitor, 2-Methoxyestradiol (2-Met), was used to evaluate its therapeutic efficacy...Pharmacological inhibition or knockdown of USP13 impedes HCC progression, induces ferroptosis, and enhances T cell-mediated cytotoxic effects. These results highlight that USP13 could be a promising therapeutic target for HCC.

Finally, 2 ME significantly inhibited the expression of Toll-like receptor-4 (TLR-4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB). In conclusion, 2 ME inhibits E. coli-induced endometritis in rats via modulation of the TLR-4/MyD88/NF-κB axis.

Furthermore, 2ME2 therapy is effective in preventing GVHD while preserving graft-versus leukemia (GVL) activity in mice. Our findings indicate that 2ME2 could be a novel and effective treatment for GVHD patients.

Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism...Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease.

Pharmacological inhibition of HIF-1α with 2-methoxyestradiol led to partial recovery of cognitive function and selectively suppressed the expression of Ccl2, a key HIF-1α-associated chemokine implicated in neuroinflammatory signaling. These findings highlight the subtype-specific vulnerability of microglia to radiation and underscore the central role of HIF-1α-mediated transcriptional changes in RIBI. Targeting the microglial HIF-1α-Ccl2 axis may thus offer a promising strategy to mitigate late-onset cognitive dysfunction following cranial irradiation.

The findings suggest that combining OVs with MTAs, specifically EHDV-TAU and 2ME2, may exploit the enhanced susceptibility of cell-cycle-perturbed cancer cells to viral infection and cell death pathways. Such combinations may improve virus-based therapies for BC and potentially other cancers.

In addition, the effects of 2-methoxyestradiol on the oxygen-sensing pathway in both hypoxic and normoxic keloid fibroblasts were evaluated. Our results suggest that 2-methoxyestradiol could be used to inhibit keloid fibroblast activity by inhibiting the oxygen-sensing pathway and its downstream effectors.

Graphene oxide flakes embroidered with 2-methoxyestradiol molecules may be a promising solution, bringing a new and important effect in the form of improving the bioavailability of the therapeutic substance, ie 2-ME. An appropriate dosage of GO-2-ME/rGO-2-ME, in which GO/rGO is a carrier of 2-methoxyestradiol (2-ME), can ensure effective penetration of the active substance through biological boundaries/membranes and controlled modification of cell signalling, ultimately leading to the selective elimination of malignant cells.

In the in vivo mouse model, the application of the hypoxia-inducible factor (HIF) inhibitor 2-methoxyestradiol demonstrates a promising efficacy in suppressing tumor growth and osteoclast differentiation in the bone lesions established by bone-tropic subpopulation of ER- MDA-MB-231 cell. Overall, our findings explore the complexity of phenotype and morphology in bone metastatic lesions of ER+ and ER- breast cancer, which offers a compelling rationale for leveraging HIF inhibitors to the treatment targeting skeletal complications of breast cancer bone metastases, especially for ER- tumors.