Anti-Cancer Effect of Nilotinib, Imatinib, DasatinibandPonatinibOn theMost Effective Inhibitor ofTyrosine Kinase ABL1 andThe Introduction ofBinding Energy

  • سال انتشار: 1395
  • محل انتشار: چهاردهمین همایش بیوشیمی فیزیک ایران
  • کد COI اختصاصی: CBC14_003
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 594
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نویسندگان

Seyed Mohsen Masoumian Hosseini

Student Research Committee, ShahidBeheshti university of medical sciences. Tehran. Iran

Masoud Homayouni-Tabrizi

Department of Biochemistry and Biophysics, Mashhad Branch, Islamic Azad University, Mashhad, Iran

Vahid Poresmail

epartment of Biochemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran

چکیده

The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has beenimplicated in processes of cell differentiation, cell division, cell adhesion, and stress response (1). Theactivity of ABL1 protein is negatively regulated by its SH3 domain (2), and deletion of the SH3 domainturns ABL1 into an oncogene (3, 4). Mutations in the ABL1 gene are associated with chronicmyelogenous leukemia (CML). This, in turn, allows the cell to become cancerous. The ABL protein canbe inhibited by various small molecules. One such inhibitor is imatinibmesylate, which occupies thetyrosine kinase domain and inhibits ABL s influence on the cell cycle. The second-generation ABLtyrosine-kinase inhibitors are also under development to inhibit ABL mutant s resistant to imatinib.Secondary inhibitors like nilotinib, ponatinib and dasatinib , which has the effect on tyrosine kinase ,inhibits its tyrosine kinase activity. In this study, the most effective inhibitor binding affinity inhibitorsare listed and described in terms of binding energy. Inhibitors were made using the software Gaussian,And docking with the software Moe was. The results of docking expression of anti-cancer compoundsbind this domain tyrosine kinase ABL1 protein that is between amino acids 242-493. The results of thedrug, nilotinib with a score of -8.0076 as a selective inhibitor of the best.

کلیدواژه ها

ABL1, imatinib, ponatinib, dasatinib,nilotinib, docking

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