EFNA1 (Ephrin A1)

As a final step, we demonstrated that IALCA also provides an attractive template for synthesizing new Eph antagonists. Overall, this work underscores the potential of the human gut microbiome as a reservoir of privileged chemical scaffolds for both fundamental pharmacology and therapeutic drug development.

Our investigation reveals a transcriptionally defined malignant population under IRF9 control that orchestrates immunosuppressive microenvironmental reprogramming via EFNA1-mediated signaling networks. The EFNA1-Linifanib combination may represent a potential therapeutic approach to mitigate anti-angiogenic resistance and restrain metastatic progression in colorectal carcinoma.

Our data demonstrate that PAE neither interferes with ephrin-A1-EphA2 interaction, nor significantly affects ephrin-A1-induced EphA2 activation. PAE is just one of many instances that teaches how difficult and challenging it is to identify natural compounds characterized by selectivity and specificity towards a molecular target.

In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients.

The dualistic nature of Eph/ephrin signaling underscores its translational promise as both a biomarker framework and a precision-guided therapeutic target. Combinatorial receptor-ligand modulation strategies may advance the treatment of central nervous system malignancies by exploiting the context-dependent roles of Eph/ephrin interactions.

Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular degeneration.

Moreover, its selectivity for EphA receptors may offer a safety advantage over pan-Eph inhibitors, which could disrupt physiological EphB functions. Together, these results position UniPR1449 as a promising lead compound for the development of multitarget therapies against GBM.

By coupling single-cell, bulk tissue, and exosomal transcriptomics, we elucidated the key molecular drivers of OV metastasis and established SCNN1A and EFNA1 as promising non-invasive biomarkers. This multi-omics framework provides an effective strategy for early detection and a better understanding of metastatic progression in OV.

Moreover, the cis interaction interferes with ligand binding in trans , attenuates EphA2 canonical signaling. Our results uncover a new mechanism of EphA2 regulation by its co-expressed ligand ephrin-A1 with important implications in its known roles in oncogenesis as well as other disease processes including development of cataract.

Ephrin-A1 Fc, an EPHA2 agonist, effectively mitigated gefitinib-induced cutaneous damage and inflammation, while concurrently downregulating K10, K17, IL-6, and TNF-α expression in HaCaT cells and upregulating CLDN4 expression. Gefitinib appears to induce dermal barrier dysfunction via the downregulation of EPHA2 expression.

Following the identification of an EFNA1-NTRK1 gene fusion via a cancer genome profiling test, the patient received treatment with larotrectinib. Although the initial biopsy showed positive pan-TRK staining in the prostate cancer tissue, the response to larotrectinib was limited in this case.

EFNA1 is a promising biomarker for early HNSCC screening and a potential therapeutic target.