Karen Miller-Moslin

TL;DR: Structural-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl- 3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.

TL;DR: Improved understanding of several of the factors governing regioselectivity in nickel-catalysed reductive coupling reactions of alkynes is provided and related studies have revealed that the reaction mechanism can differ substantially depending on the ligand employed.

TL;DR: This review provides a general overview of the various types of biological assays and in-vivo models that have been employed for the identification and optimization of Hh pathway inhibitors, including Smoothened and Smo inhibitors reported to date.

TL;DR: A cell-based screen performed in the laboratories identified a new class of Hh pathway inhibitors, 1-amino-4-benzylphthalazines, that act via antagonism of the Smoothened receptor that displayed a good pharmacokinetic profile and also afforded tumor regression in a genetic mouse model of medulloblastoma.

TL;DR: This new agent combines high intrinsic potency and good pharmacokinetic properties resulting in excellent efficacy in preclinical rodent tumor models of medulloblastoma.