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“INTEGRATED CONCEPT” for
INSILICO SCREENING & DRUG DESIGN
湯田 浩太郎 Kohtaro Yuta
In Silico Data, Ltd.
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
ACTIVITY, ADME, TOXICITY, PROPERTY ANALYSIS AND PREDICTION
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Application pattern of integrated concept “Integrated in silico screening”
“Integrated in silico drug design”
2
“Integrated” concept 1
Multivariate and pattern recognition From pattern analysis to scientific analysis
High classification and prediction rate by
KY-methods and Tailor made modeling
3
“Integrated” concept
O
N
O
O
Pharmacological activity
Physico chemical properties
ADME properties
Toxicity
Drug properties and compound structure
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
“Integrated” concept “Integrated” concept for drug development
Activity + ADME + Toxicity + Property
“ Integrated” concept
All drug properties shall be considered at the same time
“ Integrated” in silico screening & drug design
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
4
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Application pattern of integrated concept “Integrated in silico screening”
“Integrated in silico drug design”
2
“Integrated” concept 1
Multivariate and pattern recognition From pattern analysis to scientific analysis
High classification and prediction rate by
KY-methods and Tailor made modeling
3
Two application style of “Integrated”
In silico screening
“Integrated” concept
“Integrated in silico screening”
Multi-dimensional in silico screening
In silico drug design
“Integrated in silico drug design”
Interactive in silico drug design
“Integrated” concept
Application pattern of integrated concept
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
“Integrated” in silico screening
One-dimensional screening
one activity/compound
Multi-dimensional screening multiple activities ” ADME ” toxicities ” properties compound
Conventional approach
Next-generation approach
Application pattern of integrated concept
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Application pattern of integrated concept
“Interactive and real-time” drug design
Starting compound antibacterial Anti-infla
mmatory anticancer ・ ・ ・ ・ ・ pesticide
carcinogenicity Ames test LD50 ・ ・ ・ ・ ・ others ADME and properties Caco-2 BBB CYP LogP pKa LogD7.4
Modified compound
I
II
O
O
H
N
H
H
H
H
H
HH
H
H
H
H
I
I
O
O
H
N
H
H
H
H
H H
H
H
H
H
H
H
modification activity ADME toxicity
property
Information on different properties of different compounds is available anytime
*Check the effects of structure modifications on compound properties real-time
antibacterial Anti-inflammatory
anticancer ・ ・ ・ ・ ・ pesticide
carcinogenicity Ames test LD50 ・ ・ ・ ・ ・ others
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
4
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Application pattern of integrated concept “Integrated in silico screening”
“Integrated in silico drug design”
2
“Integrated” concept 1
Multivariate and pattern recognition From pattern analysis to scientific analysis
High classification and prediction rate by
KY-methods and Tailor made modeling
3
Black box Compounds
Activity Toxicity ADME Property Others
parameters Used parameters Objective
Information equivalence
Basic priniciple of data analysis by MVA & PR
Multivariate and pattern recognition
Relationship information
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Simple classification and scientific classification
Feature selection
Neural network
Recursive partitioning
N
A
A A
A A
A A
A A
A
N N N
N N
N N
N
N
N
A A
A
A
A
A
N A
A N
Pattern space impossible to be classified by linear discriminant
Classified by pattern space
Linear discriminant
N
A A
A A
A A
A
A A
A
N N
N
N N
N N N N
Pattern space classified by linear discriminant
N N
A A A
A A
Classified by scientific reasons
ADMEWORKS
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
S
S
S
S
S S S
S S S
S
S S
S S
S S S
S S S
S
S S
S S S
S S S
S
S
S
S U
Y=a1x1+a2x2+・・+anxn+const.
S outlier
Interpolation
Extrapolation Science based approach
S S
S
S
S
S
S
S
S S
S
S S
S S S
S S
S
S
S S
S
S
S S S
S S
S S
S
S
S S
Fitting by Neural Networks
R=0.99>R=0.70
Which is true outlier?
Linear regression line
Extrapolation
Extrapolation
No science based approach
Feature selection
ADMEWORKS
Simple fitting and scientific fitting
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
4
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
Application pattern of integrated concept “Integrated in silico screening”
“Integrated in silico drug design”
2
“Integrated” concept 1
Multivariate and pattern recognition From pattern analysis to scientific analysis
High classification and prediction rate by
KY-methods and Tailor made modeling
3
湯田 浩太郎 Kohtaro Yuta
In Silico Data, Ltd.
All Rights Reserved, Copyright (C) IN SILICO DATA, Ltd. 2012
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