HDAC-IN-35 (Compound 14) is a potent and selective inhibitor of VEGFR-2 and HDAC, exhibiting IC50 values of 13.2 μM for VEGFR-2 and 0.166 μM for HDAC6.

HDAC1:7.23 μM, VEGFR2:13.2 μM, HDAC6:0.166 μM, HDAC8:1.99 μM

HDAC-IN-35 (Compound 14), at concentrations ranging from 0 to 10 μM over a period of 48 hours, demonstrates anticancer effects across various cancer cell lines, including A549, PC-3, and SK-Hep-1, with IC50 values of 3.4, 1.9, and 3.2 μM respectively. Additionally, this compound exhibits potent anti-angiogenic activity, achieving over 50% growth inhibition (GI>50) at a concentration of 1.0 μM in human endothelial progenitor cells (EPCs) by targeting the VEGFR-2 pathway, and without evident systemic toxicity. Moderate inhibition of VEGFR-2 and the blocking of HDAC enzyme activity are key mechanisms through which HDAC-IN-35 delivers its anticancer properties. Furthermore, it concentration-dependently disrupts capillary-like tube formation in EPCs after 24 hours of treatment. In vitro assays support these findings; a Western Blot analysis revealed an increase in acetylated α-tubulin and histone H3, indicating a concentration-dependent reaction in cancer cells, along with a mild inhibition of VEGFR-2 phosphorylation in human EPCs, showcasing the compound's multifaceted anticancer and anti-angiogenic activities.