Documente Academic
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Documente Cultură
Cheminformatics
Simon Xi
Computational Sciences CoE
Pfizer Cambridge
My Background
Professional Experience
Senior Principal Scientist, Computational Sciences CoE, Pfizer
Cambridge
9-year experience in pharmaceutical research with a focused on
developing cheminformatics and bioinformatics applications for
research scientists
Education
MSc in Molecular Cell Biology in UTDallas
MSc in Software Engineering in SMU
Finishing Ph.D in Bioinformatics in Boston University
Primary Use
cholesterol
heartburn
asthma
heartburn
anticoagulant
asthma
depression
depression
hypertension
Lipitor 14 billion
annual sales
NME/$
$25
$20
$15
# NMEs
$10
$5
20
00
19
98
19
96
19
94
19
92
19
90
19
88
19
86
19
84
19
82
19
80
19
78
19
76
19
74
19
72
19
70
$0
60
40
20
0
~100
~100 Discovery
Discovery Approaches
Approaches
Millions of
Compounds Screened
Preclinical
Pharmacology
Preclinical Safety
1-2
Products
Clinical Pharmacology
& Safety
Discovery
Exploratory Development
Phase I
Idea
Full Development
Phase II
Phase III
10
11 - 15 Years
15
Drug
What is Chemoinformatics?
Use of computer and informational techniques,
applied to a range of problems in the field of chemistry.
These in silico techniques are commonly used in
pharmaceutical companies in the process of drug
discovery.
Chemistry is a visual science. Data visualization is a
key component of cheminformatics.
What is Chemoinformatics?
Atoms
Bonds
SMILES format
CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(
C3=CC=CC=C3)=C(N1CCC(O)CC(O)C
C(O)=O)C4=CC=C(F)C=C4
Compound Properties/Descriptors
1D, 2D, 3D, multi-dimensional properties
Series Classifications
Wards Clustering
ADME/Physicochemical Properties
Solubility
Chemical stability
Hydrophobicity/hydrogen bonding
potential
Intestinal mucosal cell permeation
Liver and kidney clearance
Metabolism
Transporters
Charge
Size
Protein binding
Blood-brain barrier permeation
Target cell permeation
Data Visualization
Grid View
Table View
Plot View
Heatmap View
Software Relevance
Software Usability
Software
Management
The not so
good part
N
N
R1
N
R2
N
N
R1
N
R2
Trifluoro-diaminopyrimidine
series (~200 cmpds)
Tested compounds
de
Mo
FW
R1
ng
ildi
u
B
l
Solving R-groups
contribution using
linear regression
R1
R2
Predictable Virtual
Chemical Space
5-50x
expansion
R1
R2
Enu
m er
atio
n
R2
r2=0.59
r2=0.92
r2=0.86
r2=0.83
r2=0.63
r2=0.88
More promiscuous
r2=0.85
r2=0.81
r2=0.81
r2=0.85
More selective
References
1. Agrafiotis, D. K., Lobanov, V. S. and Salemme, F. R. (2002) Combinatorial
informatics in the post-genomics ERA. Nat Rev Drug Discov. 1, 337-346
2. Lipinski, C. and Hopkins, A. (2004) Navigating chemical space for biology
and medicine. Nature. 432, 855-861
3. Paolini, G. V., Shapland, R. H., van Hoorn, W. P., Mason, J. S. and
Hopkins, A. L. (2006) Global mapping of pharmacological space. Nat
Biotechnol. 24, 805-815