Lionel Rouge

TL;DR: This elegant pair of papers demonstrates the therapeutic potential of an anti-BACE1 antibody for treating Alzheimer’s disease but also provides a strategy worthy of the ancient Greeks that could be applied to other therapeutic antibodies that require safe passage into the human brain.

TL;DR: Engineering compounds that inhibit USP7 activity by attenuating ubiquitin binding suggests opportunities for developing other deubiquitinase inhibitors and may be a strategy more broadly applicable to inhibiting proteins that require ubiquit in binding for full functional activity.

TL;DR: Chemical optimization of arylomycins results in an inhibitor of bacterial type I signal peptidase that shows activity both against multidrug-resistant clinical isolates of Gram-negative bacteria in vitro and in several in vivo infection models.

TL;DR: The discovery of 2 (GDC-0980), a class I PI3K and mTOR kinase inhibitor for oncology indications, has demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer.

TL;DR: The crystal structure of poliovirus receptor (PVR)/Nectin-like-5/CD155) in complex with its cognate immunoreceptor ligand T-cell-Ig- and-ITIM-domain (TIGIT) is reported and the TIGIT/PVR interface reveals a conserved specific “lock-and-key” interaction.