The main purpose of this study is to evaluate how much of the study drug (LY3372689), administered as a single dose that has the radioactive substance 14C incorporated into it, passes from blood into urine, feces and expired air in healthy male participants. The study will also measure how much of the study drug gets into the bloodstream, how its broken down, and how long it takes the body to get rid of it. The study will last about 4 weeks. Screening is required within 28 days prior to the start of the study and follow up is required approximately 7 days after discharge.

Start Date24 Feb 2023

Sponsor / Collaborator

Eli Lilly & Co.

NCT05063539 / Active, not recruitingPhase 2

Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease

The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with early symptomatic Alzheimer's Disease

Start Date16 Sep 2021

Sponsor / Collaborator

Eli Lilly & Co.

NCT04392271 / CompletedPhase 1

Assessment of Brain O-GlcNAcase (OGA) Enzyme Occupancy After Multiple Oral Doses of LY3372689 as Measured by Positron Emission Tomography (PET) With the Radioligand [18F]LY3316612 in Healthy Subjects

This study uses imaging to evaluate how LY3372689 binds to a protein in the brain. This study will be conducted in healthy participants and will last up to about 10 weeks. Screening must be completed within four weeks prior to enrollment.

Start Date06 Aug 2020

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Beta-N-acetylhexosaminidase x Enzymes

100 Translational Medicine associated with Beta-N-acetylhexosaminidase x Enzymes

0 Patents (Medical) associated with Beta-N-acetylhexosaminidase x Enzymes

277

Literatures (Medical) associated with Beta-N-acetylhexosaminidase x Enzymes

01 Sep 2024·Pest Management Science

A fungal pathogen secretes a cell wall‐associated β‐N‐acetylhexosaminidase that is co‐expressed with chitinases to contribute to infection of insects

Article

Author: Lu, Zhuoyue ; Bai, Yuting ; Luo, Zhibing ; Zhao, Xin ; Zhang, Yongjun ; Wang, Huifang ; Zhu, Qiankuan ; Peng, Xinxin

AbstractBACKGROUNDβ‐N‐acetylhexosaminidases (HEXs) are widely distributed in fungi and involved in cell wall chitin metabolism and utilization of chitin‐containing substrates. However, details of the fungal pathogens‐derived HEXs in the interaction with their hosts remain limited.RESULTSAn insect nutrients‐induced β‐N‐acetylhexosaminidase, BbHex1, was identified from the entomopathogenic fungus Beauveria bassiana, which was involved in cell wall modification and degradation of insect cuticle. BbHex1 was localized to cell wall and secreted, and displayed enzyme activity to degrade the chitinase‐hydrolyzed product (GlcNAc)2. Disruption of BbHex1 resulted in a significant decrease in the level of cell wall chitin in the presence of insect nutrients and during infection of insects, with impaired ability to penetrate insect cuticle, accompanying downregulated cell wall metabolism‐involved and cuticle‐degrading chitinase genes. However, the opposite phenotypes were examined in the gene overexpression strain. Distinctly altered cell wall structures caused by BbHex1 mutation and overexpression led to the easy activation and evasion (respectively) of insect immune response during fungal infection. As a result, BbHex1 contributed to fungal virulence. Bioinformatics analysis revealed that promoters of some co‐expressed chitinase genes with the BbHex1 promoter shared conserved transcription factors Skn7, Msn2 and Ste12, and CreA‐binding motifs, implying co‐regulation of those genes with BbHex1.CONCLUSIONThese data support a mechanism that the fungal pathogen specifically expresses BbHex1, which is co‐expressed with chitinases to modify cell wall for evasion of insect immune recognition and to degrade insect cuticle, and contributes to the fungal virulence against insects. © 2024 Society of Chemical Industry.

12 Sep 2023·Analytical chemistry

Molecular Design Strategy of Protein Isoform-Specific Fluorescent Probes by Considering Molecule in Its Entirety.

Article

Author: Zhang, Feng ; Zhang, Xiaoling ; Jing, Jing ; Zhang, Xiaoli ; Wang, Yunpeng ; Cao, Yuan ; Zang, Tienan ; Zhang, Rubo

Generally, different isoforms of proteins exert separate biological functions. However, due to similar structures and identical catalysis functions, distinguishing isoforms is challenging. Summarizing a molecular design strategy has great significance in developing a protein-specific fluorescent probe. Usually, recognition of a group was deemed to be the key to a protein isoform-specific response. However, some novel literature reported that fluorophore could play a vital role in the protein isoform-specific response. It means that any part of the fluorescent probe could affect the detected properties. In this work, we report the generation of the first probe to specifically recognize HexA(β-N-acetylhexosaminidase A), Hex-C4, by adjusting the length of the linker. Hex-C4 exhibits specific recognition of HexA both in vitro and in living cells. The integration of the fluorescent spectrum and the MD (molecular dynamics) results provide two factors for the molecular design of isoform-specific fluorescent probes. One is the interaction between tetraphenyl ethylene (AIE fluorogen) and amino acid residues, and the other is the interaction between amino acid residues and the binding group. In this work, a powerful tool to detect HexA in living cells is reported for the first time. Further, a workable molecular design strategy for protein isoform-specific fluorescent probes is summarized.

01 Sep 2023·Pest Management Science

The insecticidal activity and mechanism of tebuconazole onNilaparvata lugens(Stål)

Article

Author: Ren, Zhijie ; He, Shun ; Wan, Hu ; Li, Jianhong ; Zeng, Qinghong ; Cai, Tingwei ; Li, Chengyue ; Cai, Yongfeng ; Yu, Chang

AbstractBACKGROUNDPrevious studies have shown that fungicides have insecticidal activity that can potentially be used as an insecticide resistance management strategy in the brown planthopperNilaparvata lugens(Stål). However, the mechanism that induces mortality ofN. lugensremains elusive.RESULTSIn the present study, the insecticidal activities of 14 fungicides againstN. lugenswere determined, of which tebuconazole had the highest insecticidal activity compared with the other fungicides. Furthermore, tebuconazole significantly inhibited the expression of the chitin synthase geneNlCHS1; the chitinase genesNlCht1,NlCht5,NlCht7,NlCht9, andNlCht10; and theβ‐N‐acetylhexosaminidase genesNlHex3,NlHex4,NlHex5andNlHex6; it significantly suppressed the expression of ecdysteroid biosynthetic genes as well, includingSDR,CYP307A2,CYP307B1,CYP306A2,CYP302A1,CYP315A1andCYP314A1ofN. lugens. Additionally, tebuconazole affected the diversity, structure, composition, and function of the symbiotic fungi ofN. lugens, as well as the relative abundance of saprophytes and pathogens, suggesting that tebuconazole reshapes the diversity and function of symbiotic fungi ofN. lugens.CONCLUSIONOur findings illustrate the insecticidal mechanism of tebuconazole, possibly by inhibiting normal molting or disrupting microbial homeostasis inN. lugens, and provide an important rationale for developing novel insect management strategies to delay escalating insecticide resistance. © 2023 Society of Chemical Industry.

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