AS601245 (1,3-benzothiazol-2-yl (2-{[2-(3-pyridinyl) ethyl] amino}-4 pyrimidinyl) acetonitrile) is a potent and selective JNK inhibitor developed by Applied Research Systems ARS Holding as promising neuroprotective agent. In vitro AS601245 is a potent and cell permeable ATP competitive JNK inhibitor, which has been shown to inhibit the JNK signaling pathway, promotes cell survival after cerebral ischemia. AS601245 and clofibrate have a synergistic effect in inducing cell responses and in affecting the gene expression profile in CaCo-2 colon cancer cells. AS601245 is a new potent adenosine triphosphate-competitive JNK inhibitor, provides significant protection against the delayed loss of hippocampal CA1 neurons in a gerbil model of transient global ischemia and is also neuroprotective in rats after focal cerebral ischemia. The ischemia-induced phospho-c-Jun expression is attenuated by AS601245, providing a mechanism through which AS601245 blocks the loss of neuronal cells.

WHI-P154 is an inhibitor of Janus-activated kinase JAK3. Also this drug inhibits other common kinases including EGFR, Src, Abl, VEGFR and others. WHI-P154 is potent inhibitor of glioblastoma cell adhesion and migration. Further preclinical development of WHI-P154 may provide the basis for the design of more effective adjuvant chemotherapy programs for glioblastoma multiforme. Treatment of ALK inhibitor, WHI-P154 resulted in the down-regulation of aberrant anaplastic lymphoma kinase (ALK) signaling, shrinkage of tumor, and suppression of metastasis and significantly improved survival of ALK mutant-bearing mice.

AS-605240 is a potent and selective phosphoinositide 3-kinase (PI3K) gamma inhibitor. It selectively inhibits PI3Kgamma enzymatic activity as well as PI3Kgamma-mediated signaling and chemotaxis in vitro and in vivo. It also has peripheral activity versus other PI3K isoforms. AS-605240 did not progress to clinical development although it had been described as a development candidate.

ZM 39923 HCl is an JAK1/3 inhibitor with pIC50 of 4.4/7.1 and almost no activity to JAK2 and modestly potent to EGFR. ZM39923 breaks down to form the JAK3 inhibitor ZM449829 which exhibit similar IC50 values. ZM39923 decomposes in neutral buffer to afford potent inhibition of the Janus kinase 3, and could be used as a standard Jak3 inhibitor in assays where breakdown could occur. ZM39923 is reduced by 300-fold in the presence of DTT (10 mM) in inhibiting TGM2. ZM39923 is reversible inhibitors when TGM2 is incubated with inhibitors in the absence of Ca2+. ZM39923 shows significant inhibition of crosslinking activity with IC50 of 25 nM in the absence of DTT and IC50 of 10 μM in the presence of DTT. ZM39923 prevents early death in a Drosophila Melanogaster model of a polyQ repeat disorder called Machado-Joseph Disease. M39923 inhibits the generation of AICD-FLAG and both Aβ40 and Aβ42 by purified γ-secretase in a concentration-dependent fashion with an approximate IC50 of 20 μM. ZM39923 decreases photoaffinity-labeled PS1-CTF in the presense of γ-secretase.