 |
 |
|
|
| |
Since its
installation in 2003 Graffinity's fragment based drug discovery
approach has been successfully applied to 50 target
proteins covering various target classes. Two typical case studies are
described below.
 Proterase inhibitor program ( Case A)
Identification of selective Inhibitors against
closely related hydrolytic Enzymes
( Case B) |
|
|
| Selective
Inhibitors against closely related hydrolytic Enzymes |
|
|
Two closely
related hydrolytic enzymes have been profiled using the chemical
microarray technology plattform resulting in a specific interaction
pattern. Compounds have been resynthesized and analysed in primary and
secondary assays. The program delivered specific, nanomolar compounds
in a 3 months turnaround time.
The binding pattern of two hydrolytic enzymes A and B evolving evolving
from the fingerprinting experiments against the same 9216 leadlike
compound array. The color expresses SPR signal strength and is a
measure for relative binding strength of the protein to the immobilized
array compound. Grey spots are control ligands used for internal
quality control. |
| |
Summary
The case studies show that the Graffinity's fragment based drug
discovery process with the
underlying microarray fragment screening technology allows for early
selectivity and
druggability analysis and provides chemical information at very early
stage in the discovery process.
Graffinity's fragment based drug discovery process is a highly
promising approach for the rapid discovery and
optimisation of such small molecules. Starting from low affinity
compounds, nanomolar high affinity compounds can be generated. |
|
|
|
|
|
| |
 |
|
•
Fragment screening applied
•
Hydrolytic enzymes shown to be well
suited for the platform
• Specific fingerprinting pattern
observed
• Several unique structurally diverse
fragments (mw 220-350) identified
• Activity & selectivity confirmed in
biochemical assays |
|
|
|
|
|
|
