Phase 1, Open-Label, Parallel Group Drug-Drug Interaction Study to Assess the Effect of Fluvoxamine (CYP2C19 Inhibitor), Itraconazole (CYP3A4 Inhibitor) and Paroxetine (CYP2D6 Inhibitor) on the Pharmacokinetics of ASN51 in Healthy Subjects

The drug-drug interaction study has been designed to investigate the effect of Fluvoxamine, Itraconazole and Paroxetine on the pharmacokinetics of ASN51

开始日期2024-02-22

申办/合作机构

Asceneuron SA

NCT05749848 / Completed临床1期

Open-Label Study to Assess the Disposition of [14C]-LY3372689 Following Oral Administration in Healthy Male Participants

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.

开始日期2023-02-24

申办/合作机构

Eli Lilly & Co.

NCT05725005 / Completed临床1期

A Phase 1, Open-label, Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Target Occupancy of ASN51 Following Repeated Oral Doses.

This is a phase 1, open-label, dose escalation, PET study to investigate the brain occupancy of O-GlcNAcase, and the PD response in PBMCs, after repeated doses of ASN51 in healthy subjects.

开始日期2023-01-26

申办/合作机构

Asceneuron SA

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100 项与 β-N-乙酰氨基己糖苷酶相关的临床结果

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100 项与 β-N-乙酰氨基己糖苷酶相关的转化医学

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0 项与 β-N-乙酰氨基己糖苷酶相关的专利（医药）

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539

项与 β-N-乙酰氨基己糖苷酶相关的文献（医药）

2024-09-01·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

作者: 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.

2024-07-17·Journal of Agricultural and Food Chemistry

Three-Step Enzymatic Remodeling of Chitin into Bioactive Chitooligomers

Article

作者: Planas, Antoni ; Texidó, Mònica ; Mészáros, Zuzana ; Bojarová, Pavla ; Křen, Vladimír ; Kulik, Natalia ; Petrásková, Lucie ; Slámová, Kristýna

Here we describe a complex enzymatic approach to the efficient transformation of abundant waste chitin, a byproduct of the food industry, into valuable chitooligomers with a degree of polymerization (DP) ranging from 6 to 11. This method involves a three-step process: initial hydrolysis of chitin using engineered variants of a novel fungal chitinase from Talaromyces flavus to generate low-DP chitooligomers, followed by an extension to the desired DP using the high-yielding Y445N variant of β-N-acetylhexosaminidase from Aspergillus oryzae, achieving yields of up to 57%. Subsequently, enzymatic deacetylation of chitooligomers with DP 6 and 7 was accomplished using peptidoglycan deacetylase from Bacillus subtilis BsPdaC. The innovative enzymatic procedure demonstrates a sustainable and feasible route for converting waste chitin into unavailable bioactive chitooligomers potentially applicable as natural pesticides in ecological and sustainable agriculture.

2024-03-06·Journal of Agricultural and Food Chemistry

Characterization of a GH20 β-N-Acetylhexosaminidase from Flavobacterium algicola Suitable to Synthesize Lacto-N-triose II

Article

作者: Mao, Xiangzhao ; Secundo, Francesco ; Cao, Zhuoning ; Li, Chengqiang ; Jiang, Hong

β-N-Acetylhexosaminidases have attracted much attention in the enzymatic synthesis of lacto-N-triose II (LNT2) as a backbone precursor of human milk oligosaccharides (HMOs). In this study, a novel glycoside hydrolase (GH) 20 family β-N-acetylhexosaminidase, FlaNag2353, from Flavobacterium algicola was biochemically characterized and applied to synthesize LNT2. FlaNag2353 displayed optimal activity to p-nitrophenyl N-acetyl-β-d-glucosaminide (pNP-GlcNAc) at 40 °C and pH 8.0. In addition to its excellent hydrolysis activity toward pNP-GlcNAc and chitooligosaccharides, FlaNag2353 showed trans-glycosylation activity. Under conditions of pH 9.0 and 55 °C for 2 h and utilizing 200 mM lactose and 10 mM pNP-GlcNAc, FlaNag2353 synthesized LNT2 with a conversion ratio of 4.15% calculated from pNP-GlcNAc. Moreover, when applied to LNT2 synthesis with 10 mM pNP-GlcNAc and 9.7% (w/v) industrial waste whey powder, FlaNag2353 achieved a conversion ratio of 2.39%. This study has significant implications for broadening the applications of GH20 β-N-acetylhexosaminidases and promoting the high-value utilization of whey powder.