In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis was written by Latham, Antony M.;Kankanala, Jayakanth;Fearnley, Gareth W.;Gage, Matthew C.;Kearney, Mark T.;Homer-Vanniasinkam, Shervanthi;Wheatcroft, Stephen B.;Fishwick, Colin W. G.;Ponnambalam, Sreenivasan. And the article was included in PLoS One in 2014.Computed Properties of C20H15ClN4 This article mentions the following:
Background: Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small mol. kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues. Methodol.: We have utilized a rational in silico -based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis. Conclusions: We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro . This novel synthetic mol. has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Computed Properties of C20H15ClN4).
N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives. Phthalazine and phthalazinone derivatives are important owing to their significant biological activities and pharmacological properties. Both pyridazine and phthalazine give rise to very good TREPR signals in rigid media at low temperatures.Computed Properties of C20H15ClN4
Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem