IRAK-4 inhibitors. Part II: a structure-based assessment of imidazo[1,2-a]pyridine binding.
A potent IRAK-4 inhibitor was identified through routine project cross screening. The binding mode was inferred using a combination of in silico docking into an IRAK-4 homology model, surrogate crystal structure analysis and chemical analogue SAR.
Buckley
George M
GM
UCB, Granta Park, Great Abington, Cambridge CB21 6GS, UK.
Ceska
Thomas A
TA
Fraser
Joanne L
JL
Gowers
Lewis
L
Groom
Colin R
CR
Higueruelo
Alicia Perez
AP
Jenkins
Kerry
K
Mack
Stephen R
SR
Morgan
Trevor
T
Parry
David M
DM
Pitt
William R
WR
Rausch
Oliver
O
Richard
Marianna D
MD
Sabin
Verity
V
D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D053592:Interleukin-1 Receptor-Associated Kinases