Docking Study of 3-mercapto-1,2,4-triazole Derivatives as Inhibitors for VEGFR and EGFR

2017 ◽  
Vol 68 (3) ◽  
pp. 500-503
Author(s):  
Marius Mioc ◽  
Sorin Avram ◽  
Andrei Branco Tomescu ◽  
Daniela Veronica Chiriac ◽  
Alina Heghes ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Growth Factor ◽  
Scoring Function ◽  
Growth Factor Receptor ◽  
Docking Study ◽  
Molecular Structures ◽  
Screening Process ◽  
Protein Targets ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Computer-aided drug design plays an important role in modern day drug discovery, because it provides a more specific range for active compound chemical synthesis in detriment of the traditional ways of drug discovery. Relevant studies proved that the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are important targets for inhibition, in finding new molecules with potential anticancer activity. The aim of the present study was to create a compound library and submit this set of molecules to a docking-based virtual screening process. Molecular docking was carried out using OEDocking HYBRYD, a software with an improved scoring algorithm, which uses a ligand-based scoring function. The obtained results revealed some molecular structures that showed good predicted binding affinity towards their respective protein targets.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

scholarly journals Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab

2014 ◽  
Vol 48 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Robert Königsberg ◽  
Julia Maierhofer ◽  
Tanja Steininger ◽  
Gabriele Kienzer ◽  
Christian Dittrich
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Growth Factor ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Over Expression ◽  
Single Target ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

AbstractBackground. The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF.Case report. The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented. Our patient has been receiving the combined double administration of bevacizumab and trastuzumab for more than 4 years.Conclusions. This case report shows that (a) the combined double administration of bevacizumab and trastuzumab was be clinically effective. (b) The combination of bevacizumab and trastuzumab is safe and non-toxic. (c) Bevacizumab and trastuzumab can be used as a long-term application

scholarly journals 6,7-Disubstituted-4-anilinoquinazoline: Design, Synthesis and Anticancer Activity as a Novel Series of Potent Anticancer Agents

2020 ◽  
Vol 27 (2) ◽  
pp. 209-218
Author(s):  
Fatemeh Azmian Moghadam ◽  
Mehdi Evazalipour ◽  
Hassan Kefayati ◽  
Saeed Ghasemi
Keyword(s):  
Growth Factor ◽  
Anticancer Agents ◽  
Growth Factor Receptor ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Design Synthesis ◽  
Atp Binding Site ◽  
Novel Approach ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Background: Epidermal Growth Factor Receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are responsible for several pathological conditions such as the development of different kinds of tumors. The combined inhibition of both signal transduction pathways seems to be a promising novel approach for cancer treatment. Methods: In this study, novel 4-anilinoquinazoline derivatives with various substituents on-7 position of quinazoline moiety were designed, synthesized, and evaluated for their antiproliferative activity against A431 and HU02 cell lines. Results: Compounds 8a, 8d, and 8f displayed the most potent anticancer activities against A431(IC50 = 1.78 μM, 8.25 μM, and 7.18 μM, respectively) in comparison with reference standards(erlotinib IC50=8.31 μM and vandetanib IC50=10.62 μM). Molecular docking studies proved that8a as the most potent compound could be efficiently accommodated in the ATP binding site ofEGFR and VEGFR-2 through the formation of essential hydrogen bonds between quinazolineN1 atom and the Met796 backbone of EGFR as well as the Cys919 backbone of VEGFR-2 with a distance of 1.94 Å and 1.398 Å, respectively. Conclusion: Compound 8a as the most potent compound with morpholine and 3-bromoaniline at the 7 and 4 positions of quinazoline scaffold, respectively, deserves more study and structural optimization as an anticancer agent.

scholarly journals Vascular Endothelial Growth Factor Plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism?

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
John L. Marshall
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Efficacy And Safety ◽  
First Line ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

There has been an intensive effort to develop novel therapies for the treatment of metastatic colorectal cancer (mCRC). The anti-epidermal growth factor receptor (EGFR) antibodies panitumumab and cetuximab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab have demonstrated clinical efficacy and acceptable toxicity in the treatment of mCRC as single agents or in combination with chemotherapy. Recent clinical trials have explored the efficacy and safety of treatment regimens incorporating chemotherapy in combination with bevacizumab and either panitumumab or cetuximab in patients with mCRC. Results from the BOND-2 trial, which investigated cetuximab, bevacizumab, and chemotherapy in mCRC, provided support for this therapeutic approach. Two large randomized phase 3 trials were initiated to evaluate firstline treatment of mCRC. The Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) study investigated the efficacy and safety of oxaliplatin- or irinotecan-based chemotherapy and bevacizumab with or without panitumumab; CAIRO2 assessed the efficacy and safety of capecitabine/oxaliplatin and bevacizumab with or without cetuximab. In both trials, the combination of bevacizumab, an EGFR-specific antibody, and chemotherapy in first-line treatment of mCRC was associated with increased toxicity and no improvement in patient outcome. These results suggest that these specific combinations should not be used in first-line mCRC outside investigational studies.

scholarly journals Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

2020 ◽  
Vol 295 (29) ◽  
pp. 9917-9933 ◽  
Author(s):  
Michael D. Paul ◽  
Hana N. Grubb ◽  
Kalina Hristova
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Eph Receptor ◽  
Vital Cell ◽  
Cell Processes ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that control vital cell processes such as cell growth, survival, and differentiation. There is a growing body of evidence that RTKs from different subfamilies can interact and that these diverse interactions can have important biological consequences. However, these heterointeractions are often ignored, and their strengths are unknown. In this work, we studied the heterointeractions of nine RTK pairs, epidermal growth factor receptor (EGFR)–EPH receptor A2 (EPHA2), EGFR–vascular endothelial growth factor receptor 2 (VEGFR2), EPHA2–VEGFR2, EPHA2–fibroblast growth factor receptor 1 (FGFR1), EPHA2–FGFR2, EPHA2–FGFR3, VEGFR2–FGFR1, VEGFR2–FGFR2, and VEGFR2–FGFR3, using a FRET-based method. Surprisingly, we found that RTK heterodimerization and homodimerization strengths can be similar, underscoring the significance of RTK heterointeractions in signaling. We discuss how these heterointeractions can contribute to the complexity of RTK signal transduction, and we highlight the utility of quantitative FRET for probing multiple interactions in the plasma membrane.

Sign in / Sign up

Export Citation Format

Share Document