Vascular endothelial growth factor mRNA translational machinery (VEGF mRNA translational machinery)

The Vascular Endothelial Growth Factor (VEGF) mRNA translational machinery encompasses the cis-acting elements within the VEGF mRNA, specifically the 5' untranslated region (UTR), and the trans-acting factors such as ribosomes and RNA-binding proteins that facilitate its translation. VEGF is a critical regulator of angiogenesis, and its expression is often upregulated in hypoxic conditions within tumors via internal ribosome entry sites (IRES) (Huez et al., Mol Cell Biol, 1998). Unlike traditional VEGF inhibitors that target the secreted protein or its receptors, targeting the translational machinery prevents the production of the protein at the source (Ferrara, Nature Reviews Cancer, 2002). This approach involves small molecules that interfere with the assembly of the translational complex on the VEGF mRNA (Weetall et al., Cancer Research, 2008). By reducing VEGF levels, these therapies aim to inhibit tumor vascularization and growth. Clinical candidates like PTC299 have been developed to selectively decrease VEGF protein levels through this mechanism, although some also exhibit activity against dihydroorotate dehydrogenase (DHODH) (PTC Therapeutics, 2024; Lulla et al., 2021). This target is particularly relevant in oncology and ophthalmology, where excessive VEGF production drives disease progression.

Other names

VEGF 5' UTRVEGF translation initiation complexVEGF IRESVascular endothelial growth factor messenger RNA translation system

Inhibition of VEGF protein synthesis by targeting the 5' untranslated region (UTR) of the VEGF mRNA, thereby preventing the assembly or activity of the translational machinery (Weetall et al., 2008).