Richard A. Westhouse

TL;DR: A novel animal model that involves transgenic expression of a fusion receptor that is constitutively activated by homodimerization is described that should provide new opportunities for further understanding how aberrant IGF-IR signaling leads to tumorigenesis and for optimizing novel antagonists of the receptor kinase.

TL;DR: Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors selected as a candidate for clinical evaluation.

TL;DR: The evolution of the strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose is outlined.

TL;DR: It is found that CXCL10 was necessary and sufficient for IFN‐γ–primed human monocytes to induce a robust production of proinflammatory cytokines, such as IL‐12 and IL‐23, and targeting CXCR3 receptor engagement and p38 MAPK signaling pathways is an attractive approach to treating inflammatory diseases that are driven by innate and adaptive immunity.

TL;DR: Results are consistent with a CYP11A1-mediated bioactivation to generate a reactive species, covalent binding to proteins, and subsequently rat adrenal toxicity, and cross-species adrenaloxicity potential of this compound and related analogues.