Panzem (2-methoxyestradiol)

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.

2ME2 inhibits triple negative breast cancer by impacting major cellular processes like proliferation, apoptosis, metastasis, etc. It further modifies gene expression by altering the miRNome of triple negative breast cancer cells. Overall, our findings suggest 2ME2 as a potent anti-cancer drug for the treatment of TNBC.

While the findings highlight a promising therapeutic approach, the lack of in vivo or clinical data limits direct clinical application. Future research should focus on validating these results in animal models and exploring long-term efficacy and molecular mechanisms.

While the findings highlight a promising therapeutic approach, the lack of in vivo or clinical data limits direct clinical application. Future research should focus on validating these results in animal models and exploring long-term efficacy and molecular mechanisms.