We describe the biological properties of NVP-AUY922, a novel resorcinylic isoxazole amide
heat shock protein 90 (HSP90) inhibitor. NVP-AUY922 potently inhibits HSP90 (K d = 1.7 …

Extensive evidence implicates activation of the lipid phosphatidylinositide 3-kinase (PI3K)
pathway in the genesis and progression of various human cancers. PI3K inhibitors thus have …

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and
inhibitors offer considerable therapeutic potential. We previously described the promising …

Purpose: To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated
protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major …

There is unmet need for chemical tools to explore the role of the Mediator complex in
human pathologies ranging from cancer to cardiovascular disease. Here we determine that …

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment
of FLT3-ITD+ acute myeloid leukaemia (AML). The paucity of valid pre-clinical models …

The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in
human disease, particularly in colorectal cancer where it has been reported as a putative …

Purpose: The effective treatment of ovarian cancer is hampered by the development of drug
resistance, which may be mediated by members of the Bcl-2 family of apoptosis regulators. …

Purpose: Many tumors exhibit defective cell-cycle checkpoint control and increased replicative
stress. CHK1 is critically involved in the DNA damage response and maintenance of …

Purpose: Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases
including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers…