Garson Tsang

TL;DR: The structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity, and a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily are described, demonstrating that BRAF-mutant melanomas are highly dependent on B- RAF kinases activity.

TL;DR: Treating tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients, and the most common adverse events included fatigue, change in hair color, nausea, dysgeusia, and periorbital edema.

TL;DR: It is found that microglial depletion in a mouse model of Alzheimer’s disease impairs plaque formation and that Aβ-induced changes in neuronal gene expression are microglia-mediated.

TL;DR: Next-generation RAF inhibitors are identified (dubbed ‘paradox breakers’) that suppress mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation, a concept currently undergoing human clinical evaluation with PLX8394.

TL;DR: The first cocrystal structure of FLT3 with the TKI quizart inib is reported, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved Asp-Phe-Gly motif in the activation loop.