scholarly journals An In Silico Model for Interpreting Polypharmacology in Drug–Target Networks

2013 ◽  
pp. 67-80 ◽  
Author(s):  
Ichigaku Takigawa ◽  
Koji Tsuda ◽  
Hiroshi Mamitsuka
Keyword(s):  
In Silico ◽  
Drug Target ◽  
In Silico Model

Usefulness of collaboration between mathematical models and cell engineering for elucidating complex disease mechanisms and discover effective drugs

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Kohjitani ◽  
A Kashiwa ◽  
T Makiyama ◽  
F Toyoda ◽  
Y Yamamoto ◽  
...  
Keyword(s):  
Mathematical Model ◽  
In Silico ◽  
Complex Disease ◽  
Ion Selectivity ◽  
Public Institution ◽  
Cell Engineering ◽  
Funding Source ◽  
Patch Clamp Technique ◽  
In Silico Model

Abstract Background A missense mutation, CACNA1C-E1115K, located in the cardiac L-type calcium channel (LTCC), was recently reported to be associated with diverse arrhythmias. Several studies reported in-vivo and in-vitro modeling of this mutation, but actual mechanism and target drug of this disease has not been clarified due to its complex ion-mechanisms. Objective To reveal the mechanism of this diverse arrhythmogenic phenotype using combination of in-vitro and in-silico model. Methods and results Cell-Engineering Phase: We generated human induced pluripotent stem cell (hiPSC) from a patient carrying heterozygous CACNA1C-E1115K and differentiated into cardiomyocytes. Spontaneous APs were recorded from spontaneously beating single cardiomyocytes by using the perforated patch-clamp technique. Mathematical-Modeling Phase: We newly developed ICaL-mutation mathematical model, fitted into experimental data, including its impaired ion selectivity. Furthermore, we installed this mathematical model into hiPSC-CM simulation model. Collaboration Phase: Mutant in-silico model showed APD prolongation and frequent early afterdepolarization (EAD), which are same as in-vitro model. In-silico model revealed this EAD was mostly related to robust late-mode of sodium current occurred by Na+ overload and suggested that mexiletine is capable of reducing arrhythmia. Afterward, we applicated mexiletine onto hiPSC-CMs mutant model and found mexiletine suppress EADs. Conclusions Precise in-silico disease model can elucidate complicated ion currents and contribute predicting result of drug-testing. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists

scholarly journals A corneal-PAMPA-based in silico model for predicting corneal permeability

2021 ◽  
pp. 114218
Author(s):  
Anna Vincze ◽  
Gergö Dargó ◽  
Anita Rácz ◽  
György T. Balogh
Keyword(s):  
In Silico ◽  
Corneal Permeability ◽  
In Silico Model

Development of a predictive in silico model for mixtures of azole fungicides acting on the skeletal craniofacial AOP

2017 ◽  
Vol 280 ◽  
pp. S287
Author(s):  
Maria Battistoni ◽  
Luca Palazzolo ◽  
Frederic Yves Bois ◽  
Francesca Di Renzo ◽  
Ivano Eberini ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Model ◽  
Azole Fungicides

An in silico model to predict renal clearance of xenobiotics in humans

2015 ◽  
Vol 238 (2) ◽  
pp. S165-S166
Author(s):  
M. Atari ◽  
S. Thomas
Keyword(s):  
Renal Clearance ◽  
In Silico ◽  
In Silico Model

scholarly journals Automatic Optimization of an in Silico Model of Human iPSC Derived Cardiomyocytes Recapitulating Calcium Handling Abnormalities

2018 ◽  
Vol 9 ◽  
Author(s):  
Michelangelo Paci ◽  
Risto-Pekka Pölönen ◽  
Dario Cori ◽  
Kirsi Penttinen ◽  
Katriina Aalto-Setälä ◽  
...  
Keyword(s):  
In Silico ◽  
Calcium Handling ◽  
In Silico Model ◽  
Automatic Optimization ◽  
Human Ipsc
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