Computational Design of Multi-target Kinase Inhibitors

2018 ◽  
pp. 385-394
Author(s):  
Sinoy Sugunan ◽  
G. K. Rajanikant
Keyword(s):  
Kinase Inhibitors ◽  
Computational Design

scholarly journals Computational Design of Targeted Inhibitors of Polo-Like Kinase 1 (Plk1)

2012 ◽  
Vol 6 ◽  
pp. BBI.S8971 ◽  
Author(s):  
Krupa S. Jani ◽  
D.S. Dalafave
Keyword(s):  
Small Molecules ◽  
Kinase Inhibitors ◽  
Computational Design ◽  
Structural Features ◽  
Docking Studies ◽  
Unique Region ◽  
Atp Binding Site ◽  
Optimal Drug ◽  
Targeted Inhibitors ◽  
Specific Inhibitors

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.

The influence of tyrosine kinase inhibitors on term and preterm parturition in mice

1998 ◽  
Vol 5 (1) ◽  
pp. 60A-60A ◽  
Author(s):  
J MIJOVIC ◽  
D OLSON ◽  
T ZAKAR
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors

Lessons learned from the optimization of natural product based kinase inhibitors through molecular calculations

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
V Myrianthopoulos ◽  
P Magiatis ◽  
AL Skaltsounis ◽  
L Meijer ◽  
E Mikros
Keyword(s):  
Natural Product ◽  
Kinase Inhibitors ◽  
Lessons Learned ◽  
Molecular Calculations

Signal transduction therapy of colon tumors with multiple target kinase inhibitors

2009 ◽  
Vol 47 (05) ◽  
Author(s):  
G Kéri ◽  
L Őrfi ◽  
Z Greff ◽  
Z Varga ◽  
B Szokol ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Kinase Inhibitors ◽  
Multiple Target ◽  
Colon Tumors ◽  
Signal Transduction Therapy

Effects of multi-kinase inhibitors on pulmonary vascular and right ventricular remodelling

Pneumologie ◽  
2011 ◽  
Vol 65 (S 01) ◽  
Author(s):  
B Kojonazarov ◽  
A Sydykov ◽  
H Luitel ◽  
D Kosanovic ◽  
S Pullamsetti ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Kinase Inhibitors ◽  
Ventricular Remodelling

Side effects of tyrosine kinase inhibitors (TKIs) on bone remodelling

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
JT Tauer ◽  
A Ulmer ◽  
LC Hofbauer ◽  
M Suttorp
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Bone Remodelling

A framework for risk stratification in EGFR+ lung adenocarcinoma treated with tyrosine kinase inhibitors

2019 ◽  
Author(s):  
P Christopoulos ◽  
M Kirchner ◽  
F Bozorgmehr ◽  
N Magios ◽  
AL Volckmar ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors
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