Angela Hayes

TL;DR: Thieno[3,2-d]pyrimidine derivatives prepared and evaluated as inhibitors of PI3 kinase p110alpha resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor ofPI3K and is currently being evaluated in human clinical trials for the treatment of cancer.

TL;DR: The data show that NVP-AUY922 is a potent, novel inhibitor of HSP90, acting via several processes (cytostasis, apoptosis, invasion, and angiogenesis) to inhibit tumor growth and metastasis.

TL;DR: The structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold are described and analogues from this series have high affinity for HSp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines.

TL;DR: Despite its rapid in vivo metabolism, PI103 is a valuable tool compound for exploring the biological function of class I PI3K and importantly represents a lead for further optimization of this novel class of targeted molecular cancer therapeutic.

TL;DR: GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% antiproliferative concentrations for >8 hours following 150 mg/kg p.o.d. and sustained phosphatidylinositide 3-kinase pathway inhibition.