As a critical component in the PI3K/AKT/mTOR pathway, AKT has become an attractive target for therapeutic intervention. ARQ 092 and a next generation AKT inhibitor, ARQ 751 are selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors that potently inhibit phosphorylation of AKT. Biochemical and cellular analysis showed that ARQ 092 and ARQ 751 inhibited AKT activation not only by dephosph...

A somatic activating mutation in AKT1, c.49G>A, pGlu17Lys, that results in elevated AKT signaling in mutation-positive cells, is responsible for the mosaic overgrowth condition, Proteus syndrome. ARQ 092 is an allosteric pan-AKT inhibitor under development for treatment in cancer. We tested the efficacy of this drug for suppressing AKT signaling in cells and tissues from patients with Proteus s...

Session 1 was classified, and began with a presentation by Weatherington on various platforms in use by the US DoD, their signal collection types (described as EO & IR, although IR in general is considered an EO technology, so EO may refer to visible in this case), and growth plans for future capabilities. Fenner Milton then presented on tests by the US Army Night Vision and Electronic Sensors ...

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The AKT pathway is activated in almost half of HCC cases and in addition, long term exposure to conventional drug treatment of HCC, sorafenib, often results in over-activation of AKT, leading to HCC resistance. Therefore, it is important to assess the safety and the efficacy of selective allosteric AKT inhibito...

Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in m...

Thiocoraline (1) is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp. L-13-ACM2-092. Its structure was elucidated to be a novel cyclic thiodepsipeptide on the basis of spectroscopic methods.