1392817-33-2Relevant academic research and scientific papers
Substituted Bicyclic Pyrimidine Compounds with Tubulin and Multiple Receptor Inhibition
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, (2015/10/28)
This invention provides substituted bicyclic pyrimidine compounds and pharmaceutically acceptable salts, hydrates, and solvates of the compounds, each having tubulin and multiple receptor inhibition properties. Methods of treating a patient diagnosed with
Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential
Gangjee, Aleem,Pavana, Roheeth Kumar,Ihnat, Michael A.,Thorpe, Jessica E.,Disch, Bryan C.,Bastian, Anja,Bailey-Downs, Lora C.,Hamel, Ernest,Bai, Rouli
supporting information, p. 480 - 484 (2014/06/09)
Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI50 values of 10-7 M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and β-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.
