Hanne Merritt

Targeting IRF5 with selective covalent oral small molecules attenuates Type I IFN and pro-inflammatory cytokine secretion in human PBMCs and in mice 2309520

Shireen Khan, Sean Poust, Joselyn Del Cid, Zixiang Fang et autres

Abstract Introduction Interferon regulatory factor 5 (IRF5) is an undrugged transcription factor strongly associated with autoimmune diseases including systemic lupus erythematosus (SLE), Sjögren’s syndrome, and rheumatoid arthritis. In those diseases IRF5 is dysregulated, causing proinflammatory cytokine and Type I interferon (IFN) secretion, …

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Bioluminescent Assay for the Quantification of Cellular Glycogen Levels

Donna Leippe, Rebeca Choy, Gediminas Vidugiris, Hanne Merritt et autres

Glycogen is a large polymer of glucose that functions as an important means of storing energy and maintaining glucose homeostasis. Glycogen synthesis and degradation pathways are highly regulated and their dysregulation can contribute to disease. Glycogen storage diseases are a set of …

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A Bioluminescent Assay for Quantification of Cellular Glycogen Levels

Donna Leippe, Rebeca Choy, Gediminis Vidugiris, Hanne Merritt et autres

Glycogen is a large polymer of glucose that functions as an important means of storing energy and maintaining glucose homeostasis. Glycogen synthesis and degradation pathways are highly regulated and their dysregulation can contribute to disease. Glycogen storage diseases are a set of …

us (code pays fourni par la source)

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders

Julie C. Ullman, Kevin T. Mellem, Yannan Xi, Vyas Ramanan et autres

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule …

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Abstract 4945: Inhibition of wild-type PI3Kα signaling is required for durable efficacy in PI3Kα mutant cancer cells due to robust re-activation of wild-type PI3Kα signaling

John R. MacDougall, Mengqi Zhong, Hanne Merritt, Joselyn S. Del Cid et autres

Abstract PI3Kα is the most mutated oncogene with a high mutation rate in breast, lung, colorectal, gastric, bladder, and other tumor types. However, current inhibitors have had little efficacy in the clinic due to their inability to achieve maximal PI3Kα target engagement …

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Small molecule inhibition of glycogen synthase 1 restores autophagolysosomal and metabolic pathway dysfunction in a mouse model of Pompe disease

Julie C. Ullman, Yannan Xi, Kevin T. Mellem, Hanne Merritt et autres

The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex

Nathan M. Fastman, Yuxi Liu, Vyas Ramanan, Hanne Merritt et autres

Glycogen is the primary energy reserve in mammals, and dysregulation of glycogen metabolism can result in glycogen storage diseases (GSDs). In muscle, glycogen synthesis is initiated by the enzymes glycogenin-1 (GYG1), which seeds the molecule by autoglucosylation, and glycogen synthase-1 (GYS1), which …

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In-vitro characterization of MZE001, an orally active GYS1 inhibitor to treat Pompe disease

Rebeca Choy, Daniel Reiton, Hanne Merritt, Tarunmeet Gujral et autres

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Substrate reduction therapy for Pompe disease: Small molecule inhibition of glycogen synthase 1 in preclinical models

Julie C. Ullman, Kevin T. Mellem, Yannan Xi, Terrence F. Satterfield et autres

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Pharmacology of small molecule inhibitors of GYS1 in a mouse model of Pompe disease

Yannan Xi, Terrence F. Satterfield, Rebeca Choy, Tarunmeet Gujral et autres

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Two Distinct Mechanisms of Inhibition of LpxA Acyltransferase Essential for Lipopolysaccharide Biosynthesis

Wooseok Han, Xiaolei Ma, Carl J. Balibar, Christopher M. Rath et autres

The lipopolysaccharide biosynthesis pathway is considered an attractive drug target against the rising threat of multi-drug-resistant Gram-negative bacteria. Here, we report two novel small-molecule inhibitors (compounds 1 and 2 ) of the acyltransferase LpxA, the first enzyme in the lipopolysaccharide biosynthesis pathway. …

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Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Wooseok Han, Xiaolei Ma, Carl J. Balibar, Christopher M. Rath et autres

The paper with the doi 10.1101/850305 has been removed as a result of a technical error. The paper is available on bioRxiv under this doi: 10.1101/2019.12.14.850305.

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