Learn More
First generation EGFR TKIs (gefitinib, erlotinib) provide significant clinical benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients' disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition(More)
Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and(More)
Aberrant expression or activity of epidermal growth factor receptor (EGFr) or the closely related p185(erbB2) can promote cell proliferation and survival and thereby contribute to tumorigenesis. Specific antibodies and low molecular-weight tyrosine kinase inhibitors of both proteins are in clinical trials for cancer treatment. CP-654577 is a potent(More)
Ensemble simulations are a promising technique for identifying the signal of atmospheric response to extra-tropical sea surface temperature variability with high statistical significance. The basic idea is to perform multiple simulations from slightly different initial conditions and then to study the average signal of the ensemble. A significant obstacle(More)
This article introduces our research efforts to build the Essex Rovers’01 robot soccer team participated in the RoboCup-2001 competition. A modular design for implementing a behavior-based hierarchy is introduced, which consists of three modules such as Perception module, Cognition module and Action module. This architecture is used for the team to achieve(More)
PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for a structurally differentiated back-up candidate to PF-04691502, which is currently in phase I/II clinical trials for treating solid tumors, a lead optimization effort was carried out with a tricyclic(More)
The title compound, C(12)H(15)N(5)OS, was obtained by reaction of 2-(2-(methyl-thio)pyrimidin-4-yl)-3-oxopropane-nitrile with (tetra-hydro-furan-3-yl)hydrazine dihydro-chloride, and the racemic product was subsequently separated by chiral chromatography (first peak; [α](D) (20) = +51.3°). The chiral center at the substituted atom of the tetra-hydro-furanyl(More)
The title compound, C(13)H(17)N(5)OS, was obtained by cyclo-addition of 2-[2-(methyl-sulfan-yl)pyrimidin-4-yl]-3-oxo-propane-nitrile with (tetra-hydro-furan-3-yl)hydrazine dihydro-chloride and subsequent N-methyl-ation of 4-[2-(methyl-sulfan-yl)-pyrimidin-4-yl]-1-(tetra-hydro-furan-2-yl)-1H-pyrazol-5-amine with methyl iodide. The two mol-ecules in the(More)
Rao M. Adibhatla Bernard W. Agranoff Harish C. Agrawal Karl E. Akerman Jan Albrecht Syed F. Ali Spyridon G.A. Alivisatos* Robert Altman Luciano Angelucci Susumu Ando Brian G. Ansell* Stanley Appel Morris H. Aprison Sidney Auerbach Lawrence Austin* Ada Azaryan Efrain C. Azmitia Benjamin A. Bahr Vladimir J. Balcar Naren L. Banik Giles Barbin Jack D. Barchas(More)