Global energy and molecular interactions between Pazopanib, Axitinib and Sorafenib anticancer drugs with vascular endothelial growth factor

Abstract

Pazopanib and axitinib are ATP-competitive inhibitors of the vascular endothelial growth factor receptor. They have shown to be effective and tolerable treatment options for patients with metastatic renal cell cancer and therefore have been used for the control of this disease. Sorafenib is a kinase inhibitor drug approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. Global energy, binding sites and molecular interactions between pazopanib, sorafenib and axitinib anticancer drugs with vascular endothelial growth factor (VEGF) was probed to find the best binding energy. The structures of pazopanib, axitinib and sorafenib were drawn and constructed using window based program of Arguslab and ACDlab ChemSketch softwares. Docking studies were performed using the Patch dock and Firedock online software packages. The protein data bank (PDB) files of the crystal structure of VEGF were subjected to refinement protocols. The interactive docking method was carried out for all the conformers of each compound in the selected active site. The docked compound was assigned a score according to its fit in the ligand binding pocket (LBP) and its binding mode. The docked complexes were interpreted using Molecular Molegro viewer software. The best binding energy (minimum energy) is-19.15 Kcal/mol,-22.48 Kcal/mol and-22.37 Kcal/mol for pozapanib, sorafenib and axitinid respectively. The negative value of the binding energy shows that pozapanib, sorafenib and axitinib can selectively inhibit VEGF.

Substituted Tetrahydronaphthalen‐1‐yl‐phenethyl Ureas: Synthesis, Characterization, and Biological Evaluations

“…Many anticancer drugs have been produced as a result of intensive biological activity research, especially on urea derivatives. For example, the urea drug Sorafenib ( 1 ), commercially known as Nexavar, is a kinase inhibitor drug, which is approved for thyroid, advanced primary liver and kidney cancer treatments, [11] Lenvatinib ( 2 ) (trade name Lenvima) is an anti‐cancer drug used in the treatment of thyroid cancer [12] . Tivozanib ( 3 ), also known as Fotivda, is a drug that is used to treat advanced renal cell carcinoma that has relapsed or become refractory (RCC) [13] .…”