جستجوی مقالات مرتبط با کلیدواژه « Kinase domain » در نشریات گروه « پزشکی »

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer in which three hormone receptors are negative. This work aimed at identifying customized potential molecules inhibiting epidermal growth factor receptor (EGFR) by exploring variants using the pharmacogenomics approaches.

Experimental approach: 

The pharmacogenomics approach has been followed to identify the genetic variants across the 1000 genomes continental population. Model proteins for the populations have been designed by including genetic variants in the reported positions. The 3D structures of the mutated proteins have been generated through homology modeling. The kinase domain present in the parent and the model protein molecules has been investigated. The docking study has been performed with the protein molecules against the kinase inhibitors evaluated by the molecular dynamic simulation studies. Molecular evolution has been performed to generate the potential derivatives of these kinase inhibitors suitable for the conserved region of the kinase domain. This study considered variants within the kinase domain as the sensitive region and remaining residues as the conserved region.

The results reveal that few kinase inhibitors interact with the sensitive region. Among the derivatives of these kinase inhibitors molecules, the potential kinase inhibitor that interacts with the different population models has been identified .

Conclusions and implications:

 This study encompasses the importance of genetic variants in drug action as well as in the design of customized drugs. This research gives way to designing customized potential molecules inhibiting EGFR by exploring variants using the pharmacogenomics approaches.

Polo-like kinase 1(Plk1) plays an essential role in inhibiting cell proliferation and comes under the family of serine/threonine-protein kinase, which is a particular target for cancer therapy. In some clinical studies, Plk1 has been identified as a target for cancer. Currently, so many scientists are developing the Plk1 inhibitors, and they are thinking about working on them. A recent strategy for Plk1 inhibition is the development of small-molecule inhibitors, which will inhibit the Plk1 through the ATP-binding site of the Plk1. Now new generation Plk1 inhibitors being tested clinically, which are targeting the polo box domain. This review highlights the recent progress made in the development of Plk1 inhibitors as anticancer agents