Stefan Peukert

TL;DR: By identifying a drug combination that delays or even combats development of resistance when used as a first-line treatment in clinical trials, these results could ultimately improve the lives of patients with medulloblastoma or other cancers that depend on Smo for their survival.

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: 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: The design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs are described, culminating in the identification of LSZ102, a compound in clinical development for the treatment of ERα positive breast cancer.