Kinase insert domain protein receptor
Kinase insert domain protein receptor
Overview
Kinase insert domain protein receptor, more commonly known as KDR or VEGFR-2, is a receptor tyrosine kinase that serves as a major signaling receptor for vascular endothelial growth factor A (VEGFA). It is a central mediator of angiogenesis, endothelial cell proliferation, migration, and tube formation, and therefore plays a key role in vascular development and in the vascular remodeling that supports tumor growth and tissue repair.
In biomedical research, KDR is frequently studied as a therapeutic target in cancer, ischemic disease, and regenerative medicine. Because VEGF-A/VEGFR-2 signaling can be upregulated in tumors and in pro-angiogenic repair settings, KDR is often examined alongside related pathways and markers such as VEGFA, MAPK1, focal adhesion kinase, and JAK2/STAT3 signaling pathway components. Its inhibition is a common strategy in anti-angiogenic drug discovery, while its activation or normalization is explored in tissue regeneration and vascular repair.
Focus of Latest Publications
Recent publications have continued to examine Kinase insert domain protein receptor (KDR/VEGFR-2) primarily as an anti-angiogenic cancer target. Several studies focused on the design, synthesis, and biological evaluation of small-molecule VEGFR-2 inhibitors, including pyrazole-based, quinazoline-based, indolin-2-one, chalcone, and oxadiazole-containing scaffolds. These reports used a combination of in vitro cytotoxicity assays, enzyme inhibition assays, docking studies, and, in some cases, molecular dynamics simulations and ADMET profiling to assess target engagement and drug-likeness.
Across these studies, KDR was linked to anticancer activity in breast cancer, gastric cancer, lung cancer, hepatocellular carcinoma, and broader NCI-60 screening panels. One machine-learning and network pharmacology study of Schisandrin A in triple-negative breast cancer identified KDR among four prognosis-related core targets, although the strongest docking and experimental emphasis in that work was on other targets. In another in silico study of Pinellia ternata phytochemicals, KDR emerged as one of the core lung cancer-related targets, with baicalein predicted to bind KDR along with PTK2 and JAK2, supporting a proposed multi-target anti-angiogenic mechanism.
Experimental studies directly targeting KDR reported several promising lead compounds. A methoxyquinazoline sulfonamide derivative, compound 9a, showed strong VEGFR-2 inhibition, reduced HepG-2 cell migration, and was associated with decreased Akt phosphorylation, apoptosis, and G2/M arrest. Quinazolinone-based dual VEGFR-2/HDAC inhibitors also yielded a lead compound, 7d, with potent VEGFR-2 inhibition and strong anticancer activity. Similarly, piperazine-bridged indolin-2-one derivatives produced multiple VEGFR-2 inhibitors with selective cytotoxicity in breast cancer cells, and compound 10 induced G0/G1 arrest, apoptosis, and increased ROS generation.
Other publications reinforced KDR’s relevance in multi-target anticancer design. Chalcone-paracetamol hybrids identified compound 9 as a multi-target agent with significant VEGFR-2 inhibition alongside EGFR, COX-2, and tubulin-related activity. Pyrazole-oxadiazole-chalcone/oxime hybrids were also developed as dual EGFR/VEGFR-2 inhibitors, with compound 11b showing the highest potency against VEGFR-2 and inducing G2/M arrest and apoptosis. In a gastric cancer preclinical study, PB101 was evaluated as a VEGFR-1 decoy receptor intended to broaden anti-angiogenic blockade beyond VEGFR-2-related escape pathways involving VEGF-A, VEGF-B, and PlGF. Overall, these recent publications position KDR as a recurring focus in anti-angiogenic and anticancer drug discovery, especially in combination with apoptosis, cell-cycle arrest, and pathway modulation involving Akt1 and related signaling.