Petra Hillmann

TL;DR: It is shown that serine can bind to and activate human PKM2, and thatPKM2 activity in cells is reduced in response to serine deprivation, which shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.

TL;DR: The preclinical characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations, identifies 1 as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis.

TL;DR: In vitro and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, are characterized in preclinical lymphoma models and appeared as a novel and promising compound that is worth developing in the lymphoma setting.

TL;DR: The P2Y(2) receptor, which is activated by UTP, ATP, and dinucleotides, was studied as a prototypical nucleotide-activated GPCR and R272 (extracellular loop EL3) was found to play a gatekeeper role, presumably responsible for recognition and orientation of the nucleotides.

TL;DR: PQR620 inhibits mTOR kinase potently and selectively, shows antitumor effects in vitro and in vivo, and promises advantages in CNS indications due to its brain/plasma distribution ratio.