北京若生智能科技有限公司
Drug Database
AZ

aztreonam lysine (Cayston / Corus 1020 / AZLI)

✓ Approved

Gilead Sciences, Inc. · 小分子 · 小分子

什么是 aztreonam lysine？

aztreonam lysine 是一种小分子，由Gilead Sciences, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Inhaled。

药物档案

商品名Cayston, Corus 1020, AZLI
公司Gilead Sciences, Inc.
药物类别小分子
给药途径Inhaled
状态Approved
来源： ClinicalTrials.gov, Gilead Sciences, Inc.

治疗适应症

aztreonam lysine 针对 3 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Infections and infestationsRespiratory tract infection✓ Approved
Infections and infestationsPneumonia pseudomonal✓ Approved
Respiratory, thoracic and mediastinal disordersBronchiectasisPhase III

相关研究文献

PubMedNature communications2026-10-26

Higher-order epistasis drives evolutionary unpredictability toward new antibiotic resistance.

Gaszek Ilona Kamila IK, Yildiz Muhammed Sadik MS, Meng Zhaoxu Z, de la Paz Jose Alberto JA et al.

Antibiotic resistance has become a critical public health problem, rendering many antibiotics ineffective. In particular, the evolution of extended-spectrum β-lactamases (ESBLs) threatens β-lactams, the cornerstone of bacterial infection treatment. We investigated the evolution of Escherichia coli TEM-1 β-lactamase into ESBLs by constructing a combinatorially complete library of all 55,296 TEM-1 variants from 18 clinical mutations across 13 residues. We obtained over 9,000,000 fitness measurements under native (ampicillin) and non-native (aztreonam) selection. Graph-theoretic and epistatic analyses revealed that ampicillin selection produced weak epistasis and predictable evolutionary trajectories, whereas aztreonam selection induced extensive higher-order epistasis, increasing phenotypic unpredictability. Machine learning identified interpretable epistatic rules shaping these landscapes. Evolutionary statistics, including direct coupling analysis and latent generative landscapes, showed that top-performing ESBL variants followed conserved epistatic patterns observed in natural β-lactamases. Our integrated experimental-computational framework provides a foundation for predicting ESBL evolution and quantifying mutational contributions to ESBL variants.

PMID 42928083
阅读全文 →
PubMedFrontiers in molecular biosciences2026-10-26

When absence becomes functional: lysine deserts in protein regulation and evolution.

Szulc Natalia A NA

Lysine deserts-extended, continuous protein regions containing no lysine residues-occur across diverse proteomes, yet their definition, evolutionary origins and biological significance remain incompletely understood. In this Review, I examine the evidence linking local lysine depletion to protein regulation, with particular emphasis on ubiquitin- and proteasome-dependent pathways. Studies of toxin catalytic subunits and endogenous components of the ubiquitin-proteasome system show that introducing lysines at selected positions can alter ubiquitylation, protein turnover or function. These findings support a context-dependent model in which lysine deserts can limit the availability of ubiquitin acceptor sites within particular structural and enzymatic environments, rather than generally protecting entire proteins from modification or degradation. I discuss how lysine position, solvent accessibility, E3 ligase geometry and protein conformation determine the consequences of lysine introduction, and how N-terminal or non-lysine ubiquitylation as well as ubiquitin-independent proteolysis can bypass lysine depletion. I also consider the reported enrichment of lysine deserts in selected Actinobacteria and Mycobacterium phages, highlighting a testable Pup-proteasome adaptation hypothesis. Finally, I discuss potential functions beyond ubiquitylation and the methodological challenges of distinguishing selected lysine depletion from compositional bias or chance.

PMID 42928854
阅读全文 →
PubMedAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026-10-26

Histone Lactylation Drives WNK1 Expression to Promote Esophageal Squamous Cell Carcinoma Progression Through Histone H3 Ser10 Phosphorylation.

Yan Mingyang M, Fang Shaobo S, Song Yanming Y, Zhang Lei L et al.

Esophageal squamous cell carcinoma (ESCC) lacks effective targeted therapies, and how metabolic reprogramming drives oncogenic signaling remains poorly defined. Here, we identify histone H3 lysine 23 lactylation (H3K23la) as a key epigenetic mediator linking lactate accumulation to tumor progression. H3K23la is upregulated in ESCC and correlates with poor prognosis. Mechanistically, H3K23la promotes WNK lysine deficient protein kinase 1 (WNK1) transcription, which increases histone H3 Ser10 phosphorylation (p-H3S10) and enhances AKT transcription, thereby driving PI3K-AKT signaling. This defines a lactate-H3K23la-WNK1-p-H3S10-AKT axis connecting metabolism to oncogenic signaling. Importantly, pharmacological inhibition of WNK1 by CD03017 disrupts this pathway and suppresses tumor growth in vitro and in patient-derived xenograft (PDX) models. In conclusion, our findings define a metabolic-epigenetic-signaling axis in ESCC and establish WNK1 as a potential therapeutic target downstream of histone lactylation.

PMID 42928409
阅读全文 →
PubMedGels (Basel, Switzerland)2026-10-26

Room-Temperature Powder-Form Lysine-Based Organogelators for Rapid Remediation of Oil-Spill-Contaminated Water.

Peng Han-Qing HQ, Zhou Xiao-Yu XY, Liu Shuai-Ke SK, Liu Ke-Lu KL et al.

Oil spill remediation remains a major challenge in global marine pollution control. Given their rapid oil removal capability, reusability, and environmental compatibility, phase-selective organogelators (PSOGs) have become attractive candidates. Nevertheless, few powdered PSOGs have been reported to rapidly form phase-selective gels with crude oils. In this work, we synthesized a series of lysine-derived organogelators (Lys-OUAs) through a simple route and evaluated their gelation behavior. In particular, Lys-OUA-C14 showed superior gelation ability and formed stable gels with a wide range of petroleum hydrocarbons. Results obtained from Fourier-transform infrared spectroscopy, UV-vis absorption spectroscopy, scanning electron microscopy, concentration-dependent and temperature-dependent 1H NMR, differential scanning calorimetry, and X-ray diffraction indicated that van der Waals forces, hydrogen bonding, and π-π stacking interactions were involved in the self-assembly of Lys-OUA-C14. Notably, Lys-OUA-C14 rapidly solidified diesel and enabled efficient recovery within 120 s through three-dimensional networks, without the need for external heating/cooling cycles or co-solvents. Powdered Lys-OUA-C14 can be readily synthesized in high yield and exhibits good oil removal efficiency, outstanding recyclability, and eco-friendliness, making it a promising material for large-scale remediation of oil-spill-contaminated water.

PMID 42929919
阅读全文 →
PubMedFrontiers in cell and developmental biology2026-10-26

Lysine lactylation in glioma: from metabolic stress to epigenetic remodeling and therapeutic resistance.

Hu Xiaosong X, Yang Li L, Hu Yanghao Y, Cui Hongjuan H

Glioma is characterized by profound metabolic reprogramming and sustained lactate accumulation; however, the mechanisms by which lactate-rich metabolic stress is translated into stable malignant phenotypes remain incompletely understood. Lysine lactylation (Kla), a recently identified post-translational modification, has emerged as a critical nexus linking lactate metabolism to durable epigenetic and protein-state adaptations. In glioma, accumulating evidence indicates that Kla contributes to multiple dimensions of tumor biology, including oncogenic transcriptional activation, glioma stem-like cell (GSC) maintenance, immunosuppressive remodeling, and therapeutic resistance. Mechanistically, histone Kla rewires metabolic stress-responsive transcriptional programs, whereas non-histone Kla executes rapid, transcription-independent responses by directly modifying key regulatory proteins involved in DNA repair, signal transduction, and metabolic adaptation. This review systematically summarizes current progress on the lactate-Kla axis in glioma, encompassing the basis of lactate metabolism, the molecular regulatory network of Kla, and the distinct yet coordinated functions of histone and non-histone lactylation. We further discuss how Kla contributes to temozolomide (TMZ) resistance, radioresistance, and chemoradiotherapy adaptation, and outline a hierarchical therapeutic framework targeting this pathway. Despite rapid advances, important areas requiring further investigation include subtype-specific variation in lactate-Kla biology and the potential crosstalk between Kla and other post-translational modifications. A better understanding of these issues will help define the biological significance of the lactate-Kla axis and guide the future development of lactylation-based therapeutic strategies in glioma.

PMID 42928918
阅读全文 →
PubMedBiotech (Basel (Switzerland))2026-10-26

Systematic Phosphoproteomic Analysis of Co-Differentially Associated Phosphosites Within the WNK1 C-Terminal Disordered Region.

Khan Noreen A NA, Fahma Amal A, Gopalakrishnan Athira Perunelly AP, Sambreena Alimath A et al.

With-No-Lysine Kinase 1 (WNK1) is an atypical serine/threonine kinase involved in ion homeostasis, blood pressure regulation, migration and proliferation. Its intrinsically disordered regions (IDRs) support dynamic phosphorylation patterns. Here, we compiled 895 human phosphoproteomic profiling datasets and 352 differential phosphoproteomic datasets to systematically characterise the phosphorylation landscape associated with WNK1. Among reported WNK1 phosphosites, S2027, S2029, and S2032, located within an IDR, were the most frequently detected. Using a one-sided Fisher's Exact Test followed by three sequential bias-correction filters, we identified 387 phosphosites in other proteins (PsOPs) showing positive co-differential association and 34 showing negative co-differential association with these three WNK1 sites. Computational approaches and database integration identified two candidate upstream kinases (EIF2AK1 and MAPK3), eight binary interactors, and 26 candidate substrate proteins. GO enrichment revealed site-specific functional categories: S2027-associated proteins were enriched in Ras/small GTPase signaling, chromatin organization, and cell-cycle-related processes; S2029-associated proteins in chromosome organization and transcriptional regulation; and S2032-associated proteins mainly in GTPase-related molecular functions. These findings provide a phosphosite-centric resource and computationally supported candidate associations that generate testable hypotheses for further experimental investigation of WNK1-associated signaling.

PMID 42930072
阅读全文 →

注册免费账户还可查看另外 9996 篇文献

免费注册查看全部文献 →

了解更多aztreonam lysine