Robert C. Armstrong

TL;DR: The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

TL;DR: Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile, and the dose-limiting toxicity was grade 3 QT prolongation.

TL;DR: The approach described enables investigation of the complex relationship between kinase activation state and compound binding affinity and should facilitate strategic inhibitor design.

TL;DR: A first-in-human Phase 1 study investigating AC220 in predominantly relapsed or refractory AML pts, unselected for FLT3 mutations, was recently completed, using a standard 3+3 dose escalation with 50% dose increments.

TL;DR: An SAR optimization campaign around a series of quinazoline derived BRAF(V600E) inhibitors is described, which led directly to the identification of a clinical candidate, compound 40 (CEP-32496), which exhibits high potency against several BRAf(V 600E)-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAF, versus those containing wild-type BRAF.