JNJ-7706621, developed by Johnson & Johnson Pharmaceutical, is pan-CDK inhibitor with the highest potency on cyclin-dependent kinases: CDK1/2. Inhibition of CDK1 kinase activity, altered CDK1 phosphorylation status, and interference with downstream substrates such as retinoblastoma was also shown in human tumor cells following drug treatment. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1. In human cancer cells, treatment with JNJ-7706621 inhibited cell growth independent of p53, retinoblastoma, or P-glycoprotein status; activated apoptosis; and reduced colony formation. At low concentrations, JNJ-7706621 slowed the growth of cells and at higher concentrations induced cytotoxicity. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma.

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.