IC50: 35 nM for IRAK-4
The interleukin-1 receptor associated kinase (IRAK) family is comprised of four family members IRAK-1, IRAK-2, IRAK-3/M, and IRAK-4. Upon activation of their upstream cognate receptors, IRAK-4 is thought to phosphorylate IRAK-1 resulting in the activation and autophosphorylation of IRAK-1 an subsequent phosphorylation of downstream substrates. IRAK inhibitor 1 is an inhibitor of interleukin-1 receptor associated kinase 4 (IRAK-4).
In vitro: The regioisomeric pyridines IRAK inhibitor 1 (6) and it analogue (7) showed contrasting SAR, with the 2,6-pyridine isomer IRAK inhibitor 1 having low-nanomolar potency whilst the 2,4-pyridine isomer 7 showed little activity, despite having a more accessible bidentate-binding motif. At 10 μM, IRAK inhibitor 1 was found to have 39% inhibition for JNK-1 and 15% inhibition for JNK-2, respectivley [1].
In vivo: No animal in-vivo data available currently IRAK inhibitor 1 and its analogues.
Clinical trial: IRAK inhibitor 1 is currently in the preclinical development stage and no clinical data are available.
Reference:
[1] Buckley GM, Ceska TA, Fraser JL, Gowers L, Groom CR, Higueruelo AP, Jenkins K, Mack SR, Morgan T, Parry DM, Pitt WR, Rausch O, Richard MD, Sabin V. IRAK-4 inhibitors. Part II: a structure-based assessment of imidazo[1,2-a]pyridine binding. Bioorg Med Chem Lett. 2008;18(11):3291-5.