we examine recent developments in the discovery of JNK inhibitors and their potential in treating human disease. We first concentrate on supplier AG-1478 small particle, ATP aggressive JNK inhibitors as summarised in. Our preliminary discussion centers on SP600125 manufactured by Signal Pharmaceuticals/Celgene. Furthermore, we offer a quick overview of an ever-increasing quantity of other small particle ATP aggressive JNK inhibitors now defined in the published literature. The recent advances are then discussed by us in the utilization of ATP non competitive JNK inhibitory peptides. These inhibitors are also featured in. Lastly, we consider questions that arise with the growth of JNK inhibitors and their possible therapeutic application. These questions centre on the settings had a need to establish nature of measures of JNK inhibitors, whether JNK isoformselective inhibitors are probable or desirable, Papillary thyroid cancer whether other substances have off goal effects to prevent JNK, and what issues accompany the serious use of JNK specific inhibitors. Further work will be needed seriously to address these dilemmas, however the proven effectiveness of the existing generation of JNK inhibitors in improving outcomes in illness models implies that this further work will pay dividends. In late 2001, the little particle JNK chemical, SP600125 one, was reported following a testing of a library for inhibitors of JNK2 action towards the d Jun transactivation domain. The chemical structure of SP600125 is found in, along with the buildings of other small molecule inhibitors of JNK discussed in subsequent chapters of this review. The extremely planar nature of SP600125 and poor solubility in aqueous solution, both consequences of its anthrapyrazolone core structure, were known in its original description. JNK inhibition by SP600125 was more Bicalutamide Androgen Receptor inhibitor observed to be reversible and ATP aggressive, demonstrating IC50 values for JNK inhibition in the product range of 40?90 nM with N300 fold selectivity over the related mitogen activated protein kinases, ERK1 and p38 2 and between 10 fold and 100 fold selectivity over another 14 protein kinases tested. These results suggested high affinity and specific interactions of SP600125 with elements in the JNK ATP binding site. These relationships of SP600125 with JNK have now been further explored following the co crystallisation of SP600125 with JNK3. The resulting design : 1PMV is shown in, where the JNK3 elements not preserved in the related MAPK, p38 2, have been highlighted. These remains produce a thin ATP binding pocket in JNK that met the planar SP600125 molecule and were predicted to donate to the specificity of SP600125 towards JNK on the p38 MAPKs.