Presentation of a Structurally Diverse and Commercially Available Drug Data Set for Correlation and Benchmarking Studies Anders Karlén Uppsala University O HO HO O NH 2 NH 2 H 2 N NH 2 OH O O HO OH O O HO OH NH 2 H CH 2 NH 2 H3C HO CH 3 CH3 O CH3 CH3 CH3 CH3 CH3 H2N SH O P P O HO HO HO HO OH NH 2 CH3 O H 3 C CH 3 O N O OH N H O O N O O H CH3 H3C H3C CH3 S N H3C CH3 O O
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Presentation of a Structurally Diverse and Commercially Available Drug Data Set for Correlation and Benchmarking Studies Anders Karlén Uppsala University.
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Presentation of a Structurally Diverse and Commercially Available Drug Data Set for Correlation and Benchmarking Studies
Anders KarlénUppsala University
OHOHO
O
NH2
NH2
H2N
NH2OHO
OHO
OH
OO
HOOH
NH2H CH2NH2
H3C
HO
CH3
CH3
O CH3CH3 CH3
CH3
CH3
H2NSH
O
P
P
O
HOHO
HO
HO OH
NH2CH3
O
H3C CH3
O
NO
OHNH
O
O
N
O
O
H
CH3H3C
H3C
CH3S
NH3C
CH3
OO
Aim of study
• Derive a “benchmark data set“– Drug-like– Physicochemically diverse – Commercially available and inexpensive– Amenable to analytical measurements
• Start the generation of benchmark data– Derive good-quality data from the same
lab
Possible use of the data set
• General description of drugs• Developing ADME/TOX filters
(permeability, solubility, plasma protein binding etc.)
• To validate novel experimental techniques
Generation of a ”benchmark” data set based on the list of drugs in Sweden (FASS 2001)
691 cpds
Remove compounds•Molecular weight >900•Polymers, polypeptides•Inorganic and metal containing
799 cpds 370 cpds
Select commercially available< $800/g
332 cpds
•Select only oral, nasal, pulminal, ocular, parenteral and rectal administered drugs
284 cpds
Remove “odd” ATC classese.g. A01(Mouth and teeth),A05(Bile acids)A06 (Laxative)…
Exp.design
24-compound data set
450
Cost and availability of the 691-compound data set
Sun, D. et al. Comparison of Human and Caco 2 Gene Expression Profiles for 12,000 Genes and the Permeabilities of 26 Drugs in the Human Intestine and Caco 2 Cells. Pharm Res 2002, 19, 1398-1413
4. Permeability/absorption
Low
Med
ium
Hig
h
4. Permeability/absorption In vitro Papp values in human Caco-2 cells
Suggestions on the ”Uppsala diverse data set” usage
• The 24 compounds can be used– as a test set for testing already derived models of permeability,
lipophilicity, solubility etc.– as a validation set for new experimental techniques– on its own for building and validating models by dividing it into a
training set and a test set
We hope that other groups are willing to help us to supplement the herein-started characterization