Gail L. Wrigley

TL;DR: Following observations of significant tumor inhibition in preclinical models, the clinical candidate AZD9291 was administered clinically to patients with T790M positive EGFR-TKI resistant NSCLC and early efficacy has been observed, accompanied by an encouraging safety profile.

TL;DR: It is demonstrated that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras.

TL;DR: These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimERTinib for the treatment of EG FR-mutant brain metastasis.

TL;DR: The optimized compound from this campaign exhibited excellent pharmacokinetic profile and exhibited high potency in vitro and in vivo effecting c-Myc downregulation and tumor growth inhibition in xenograft studies.

TL;DR: A workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under‐represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis).