Biological Activity
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].
References
[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.
