A Phase 1, Open-label, Single-dose Study to Determine the Safety and Pharmacokinetics of ORAvance (Ceftibuten/Xeruborbactam Oral Prodrug [QPX7831]) in Participants With Renal Impairment

A Phase 1, open-label, single-dose study to determine the safety and pharmacokinetics of ORAvance (ceftibuten/xeruborbactam oral prodrug [QPX7831]) in participants with renal impairment

开始日期2024-10-01

申办/合作机构

Qpex Biopharma, Inc.初创企业

[+2]

NCT06547554 / Recruiting临床1期

A Phase 1, Randomized, Double-blind, Placebo-controlled, Drug-drug Interaction, Pharmacokinetic, and Safety Study of Cefiderocol in Combination With Xeruborbactam in Healthy Adult Participants

A phase 1, randomized, double blind, placebo controlled drug-drug interaction, pharmacokinetics and safety study of cefiderocol in combination with xeruborbactam in healthy adult participants

开始日期2024-09-04

申办/合作机构

Qpex Biopharma, Inc.初创企业

[+2]

100 项与 Serine protease x β-lactamase 相关的临床结果

登录后查看更多信息

100 项与 Serine protease x β-lactamase 相关的转化医学

登录后查看更多信息

0 项与 Serine protease x β-lactamase 相关的专利（医药）

登录后查看更多信息

项与 Serine protease x β-lactamase 相关的文献（医药）

2022-05-01·Structure2区 · 生物学

Structural basis for the catalytic activity of filamentous human serine beta-lactamase-like protein LACTB

2区 · 生物学

Article

作者: Zhang, Minghui ; Zhang, Sensen ; Yang, Maojun ; Yin, Jian ; Xiao, Chun ; Guo, Runyu ; Zhang, Laixing

Serine beta-lactamase-like protein (LACTB) is a mammalian mitochondrial serine protease that can specifically hydrolyze peptide bonds adjacent to aspartic acid residues and is structurally related to prokaryotic penicillin-binding proteins. Here, we determined the cryoelectron microscopy structures of human LACTB (hLACTB) filaments from wild-type protein, a middle region deletion mutant, and in complex with the inhibitor Z-AAD-CMK at 3.0-, 3.1-, and 2.8-Å resolution, respectively. Structural analysis and activity assays revealed that three interfaces are required for the assembly of hLACTB filaments and that the formation of higher order helical structures facilitates its cleavage activity. Further structural and enzymatic analyses of middle region deletion constructs indicated that, while this region is necessary for substrate hydrolysis, it is not required for filament formation. Moreover, the inhibitor-bound structure showed that hLACTB may cleave peptide bonds adjacent to aspartic acid residues. These findings provide the structural basis underlying hLACTB catalytic activity.

2021-02-01·Cancer Letters1区 · 医学

LACTB promotes metastasis of nasopharyngeal carcinoma via activation of ERBB3/EGFR-ERK signaling resulting in unfavorable patient survival

1区 · 医学

Article

作者: Xu, Liang ; Liu, Zhi-Jie ; Huang, Bi-Jun ; Shu, Di-Tian ; Sun, Rui ; Luo, Fei-Fei ; Yang, Jun-Ping ; Wang, Ming-Dian ; Lang, Yan-Hong ; Meng, Dong-Fang ; Zheng, Li-Sheng ; Guo, Ling-Ling ; Qian, Chao-Nan ; Peng, Li-Xia ; Mei, Yan ; Qiang, Yuan-Yuan ; Xie, De-Huan ; Peng, Xing-Si ; Xie, Ping ; Lin, Si-Ting ; Li, Chang-Zhi

Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers. Distant metastasis is the main reason for treatment failure with the underlying mechanisms remaining unclear. By comparing the expression profiling of NPCs versus non-cancerous nasopharyngeal tissues, we found LACTB was highly expressed in the tumor tissues. We found that elevated expression of the LACTB protein in primary NPCs correlated with poorer patient survival. LACTB is known to be a serine protease and a ubiquitous mitochondrial protein localized in the intermembrane space. Its role in tumor biology remains controversial. We found that the different methylation pattern of LACTB promoter led to its differential expression in NPC cells. Overexpressing LACTB in NPC cells promoted their motility in vitro and metastasis in vivo. While knocking down LACTB reduced the metastasis capability of NPC cells. However, LACTB did not influence cellular proliferation. We further found the role of LACTB in promoting NPC metastasis depended on the activation of ERBB3/EGFR-ERK signaling, which in turn, affected the stability and the following acetylation of histone H3. These findings may shed light on unveiling the mechanisms of NPC metastasis.

2013-05-01·Journal of Antimicrobial Chemotherapy2区 · 医学

Complete sequence of broad-host-range plasmid pNOR-2000 harbouring the metallo-β-lactamase gene blaVIM-2 from Pseudomonas aeruginosa

2区 · 医学

Article

作者: Alfred Pühler ; Laurent Poirel ; Patrice Nordmann ; Felix G. Eikmeyer ; Andreas Schlüter ; Rémy A. Bonnin ; Daniel Wibberg

OBJECTIVESMetallo-β-lactamases (MBLs) are increasingly reported not only in Enterobacteriaceae but also in Pseudomonas spp. These enzymes hydrolyse all β-lactams, including carbapenems, and are not inhibited by β-lactamase inhibitors. The aim of this study was to fully characterize a plasmid bearing the blaVIM-2 MBL gene identified in a Pseudomonas aeruginosa isolate.METHODSThis plasmid was fully sequenced by high-density pyrosequencing and annotated using the GenDB version 2.0 annotation tool. The evaluation of the broad-host-range replication of the pNOR-2000 replication initiation gene was assessed using electro-transformation and conjugation assays and the distribution of this replicase gene was evaluated using an international collection of VIM-producing Pseudomonas spp.RESULTSAnalysis of the 21 880 bp sequence of pNOR-2000 revealed a truncated and non-functional transfer operon, in addition to novel genes encoding a serine protease and toxin/antitoxin addiction systems. This broad-host-range plasmid shares high gene synteny with part of the mobile genomic island pKLC102 identified in P. aeruginosa strain C.CONCLUSIONSWe report here the complete nucleotide sequence of plasmid pNOR-2000 from a P. aeruginosa clinical isolate harbouring the integron-located MBL gene blaVIM-2.