Layton H. Smith

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NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been(More)
Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 =(More)
Because excretion of certain nucleosides increases in all types of cancer, detection and treatment of the disease would be enhanced by rapid, simple quantitation of such nucleotides. To facilitate these analyses in urine, we have prepared a specific adsorbent for nucleosides. The affinity adsorbent gel contains an immobilized phenylboronic acid group that(More)
Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3(More)
Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC 50 =(More)
Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the(More)
b S Supporting Information T he mammalian innate immune system serves as a first line of defense and relies on the detection of specific microbial ligands or " pathogen-associated molecular patterns " (PAMPs) by pattern recognition molecules (PRMs), acting as microbial sensors. 1À7 In this context, among the major classes of PRMs is the NLR (NACHT and(More)
A unique series of biologically active chemical probes that selectively inhibit NF-kappaB activation induced by protein kinase C (PKC) pathway activators have been identified through a cell-based phenotypic reporter gene assay. These 2-aminobenzimidazoles represent initial chemical tools to be used in gaining further understanding on the cellular mechanisms(More)
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