بررسی کوانتومکانیکی و آنالیز کنفورماسیونی موتسانیب به عنوان یک مهارکننده قدرتمند رسپتور VEGFR-2

عبادی, احمد and میری, رامین and رزاقی اصل, نیما and شهابی پور, سارا (1393) بررسی کوانتومکانیکی و آنالیز کنفورماسیونی موتسانیب به عنوان یک مهارکننده قدرتمند رسپتور VEGFR-2. Iranian Journal of Pharmaceutical Research ــ 12 (2). pp. 405-415. شاپا 1735-0328

Text - Published Version

Official URL: http://ijpr.sbmu.ac.ir/article_1486_68.html


Ab Initio and conformational analysis of a potent VEGFR-2 inhibitor: A case study on motesanib

English Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2); a cell surface receptor for vascular endothelial growth factors, is a key pharmacological target involved in the cell proliferation/angiogenesis. It has been revealed that VEGFR-2 induces proliferation through activation of the extracellular signal-regulated kinases pathway. In this regard, targeting the VEGFR-2 has been considered as an efficient route to develop anti-tumor agents. Motesanib is a small-molecule antagonist of VEGFR-1, 2, and 3 (IC50s; 2 nM, 3 nM, 6 nM, respectively). It is an experimental drug candidate undergoing clinical trials against some types of cancer. In the present study, Motesanib (AMG 706) was evaluated in terms of its binding energies with individual amino acids of VEGFR-2 active site (amino acid decomposition analysis). For this purpose, functional B3LYP associated with split valence basis set using polarization functions (Def2-SVP) was used. Comparative conformational analysis of the ligand in optimized and crystallographic states revealed that Motesanib does not necessarily bind to the VEGFR-2 active site in its minimum energy conformer.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :احمد عبادی
نویسنده مسئول :رامین میری
نویسنده :نیما رزاقی اصل
نویسنده :سارا شهابی پور
Additional Information:Impact Factor (2014): 1.065 Indexing Databases : (ISI) Science Citation Index Expanded ، Embase ، Scopus ، BIOSIS Previews ، DOAJ (Directory of Open Access Journals) ، Index Copernicus
کلیدواژه ها (انگلیسی):VEGFR-2; Motesanib; Cancer; B3LYP; DFT
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:5393
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:18 Aug 1393 06:27
Last Modified:10 Sep 1397 11:11

Repository Staff Only: item control page

Document Downloads

More statistics for this item...