Poster
24
The determinants of kinome selectivity in
imidazo[4,5-b]pyridine fragment libraries
Jonathan Macdonald – ICR, London
Fragment Library Screening,
where are the follow up compounds?
•To rapidly explore SAR from a hit
•To explore selectivity effects
-log (IC50)
10
Drugs
LE = 1.5
9
8
HTS hits
HTS Hits
7
LeadLike Hits
6
5
4
Fragments
Key
Transition
3
Focused Fragment Libraries based on a
single heterocyclic core…
LE = 0.3
2
0
10
20
30
40
No. of heavy atoms
Key Questions:
How do different groups in different vectors affect kinome selectivity?
What factors determine the selectivity that is observed?
Can we derive a predictive model of kinome family selectivity?
50