Publications by authors named "Susan E Hill"
Article Synopsis
- SMARCA2 (BRM) is a key ATPase and member of the SWI/SNF chromatin-remodeling complex, which plays a crucial role in regulating gene expression alongside its relative, BRG1 (SMARCA4).
- Current research highlights the lack of small molecules that can specifically inhibit the ATPase activity of SWI/SNF, despite the relevance in cancer, particularly in BRG1-deficient cases.
- New allosteric dual inhibitors targeting both BRM and BRG1 have been developed, showing potential to reduce BRM-dependent gene expression and demonstrate anti-cancer effects in a BRG1-mutant lung tumor model, providing insights into SWI/SNF functions in various health contexts.
The ERK/MAPK pathway plays a central role in the regulation of critical cellular processes and is activated in more than 30% of human cancers. Specific BRAF and MEK inhibitors have shown clinical efficacy in patients for the treatment of BRAF-mutant melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the ERK signal pathway.
View Article and Find Full Text PDFA preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to have an in vitro potency similar to that of MRK-1 against the pharmacological target and were therefore thought to contribute to the observed efficacy.
View Article and Find Full Text PDFA potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques.
View Article and Find Full Text PDFBackground: Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its in vivo pharmacodynamic (PD) effects.
Methods: We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation.