Background:

hVEGF-IN-1 represses human VEGF-A translation and shows antitumor activity.

hVEGF-IN-1 shows a significant specific interaction with the G-rich region within the 5′- untranslated regions (5′-UTR) of hVEGF-A mRNA and destabilizes the Gquadruplex structure. hVEGF-IN-1 binds to the IRES-A (WT) with a Kd of 0.928 μM and binds to the hairpin DNA with a Kd of 21.2 μM. The G-rich sequence G774-G790 within the IRES-A of hVEGF-A’s 5′-UTR has been shown to be critical for the translation initiation activity of IRES-A. hVEGF-IN-1 hinders BG4 from binding to the IRES-A RNA G-quadruplex in cells. hVEGF-IN-1 down-regulates hVEGF-A’s translation via the G-quadruplex within IRES-A mRNA. hVEGF-IN-1 treatment reduces MDA-MB- 231 cell migration to approximately 25%[1].

Tumor bearing mice treated with hVEGF-IN-1 have an average tumor volume of less than 300 mm3. The tumor weight in the presence of hVEGF-IN-1 reduces around 60.1% to a final weight of 0.18 g. No significant change in body weight is observed during the treatment[1].

[1]. Discovery of Small Molecules for Repressing Cap-Independent Translation of Human VascularEndothelial Growth Factor (hVEGF) as Novel Antitumor Agents. J Med Chem. 2017 Jul 13;60(13):5306-5319.