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alpha-1 proteinase (Trypsone / Trypsan)

✓ Approved

Grifols, S.A. · SERPINA1

什么是 alpha-1 proteinase？

alpha-1 proteinase 是一种治疗药物，由Grifols, S.A.研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名Trypsone, Trypsan
公司Grifols, S.A.
分子靶点SERPINA1
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Grifols, S.A.

作用机制

分子靶点

alpha-1 proteinase 作用于 1 个分子靶点：

SERPINA1serpin family A member 1 (PRO2275, nNIF)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

alpha-1 proteinase 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Congenital, familial and genetic disordersCongenital emphysema✓ Approved

相关研究文献

PubMedMolecular biology reports2026-07-27

Aptamer-mediated targeting of CXCR3-B in acute lymphoblastic leukemia nalm-6 cells: an in silico and in vitro study.

Arezoomand Hossein H, Jebali Ali A, Valandani Hajar Mardani HM, Nooshadokht Maryam M et al.

The CXCR3-B receptor plays a crucial role in inducing apoptosis upon binding with its ligands. Here, we aimed to rationally design an ultra-short (5-base) DNA aptamer targeting the N-terminal domain of CXCR3-B and evaluate its therapeutic potential in Acute Lymphoblastic Leukemia (ALL). An in-silico library of 32 pentanucleotide aptamers (comprising adenine and guanine) was constructed. The three-dimensional structure of the CXCR3-B N-terminus was modeled and docked with the aptamers, followed by targeted molecular docking and binding stability scoring to evaluate complex interactions. In vitro, Nalm-6 cells were treated with the lead aptamer (GAGGA), a scrambled control, and proteinase K. Cell viability, metabolic activity, and apoptosis were assessed via trypan blue, MTT, and Annexin V/PI flow cytometry. The expression of BAX, P53, and CDKN1A (p21) was quantified using qPCR. The GAGGA aptamer exhibited the highest binding affinity and complex stability in silico. In vitro, GAGGA at 600 µM significantly reduced metabolic activity and viability after 24 h compared with untreated and scrambled aptamer controls. The apoptotic cell ratio increased significantly (13.65% vs. 2.98% in control), accompanied by the significant upregulation of BAX, P53, and CDKN1A. Pre-treatment with proteinase K abolished these effects, confirming receptor-specific binding. Our findings demonstrate that the ultra-short GAGGA aptamer specifically targets CXCR3-B and triggers apoptotic pathways in ALL cells. While the effective concentration is high, likely due to the lack of nuclease resistance in unmodified ultra-short oligonucleotides, this study provides a novel molecular scaffold for future aptamer-based ALL therapies following appropriate chemical modifications.

PMID 42507227
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PubMedBulletin of experimental biology and medicine2026-07-27

The Influence of Tumor Necrosis Factor Alpha on the Permeability of Nasal Epithelial Cell Monolayer.

Abalenikhina Yu V YV, Breslavets D I DI, Mylnikov P Yu PY, Builina S G SG et al.

The effect of tumor necrosis factor alpha (TNFα) on the barrier function of the nasal epithelium (RPMI 2650 cell line) was studied in in vitro experiments. It was shown that short-term exposure to the cytokine (6 h) increased transepithelial electrical resistance and decreased paracellular permeability for mannitol, which was accompanied by elevated expression of the tight junction proteins occludin and claudin-1. Prolonged exposure (48 h) caused an opposite effect, i.e., a significant decrease in the barrier function and a decrease in the content of the studied proteins. These results indicate that the proinflammatory cytokine TNFα modulates the permeability of the nasal epithelium, which should be taken into account when developing strategies for intranasal drug delivery.

PMID 42507093
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PubMedAutophagy2026-07-27

Autophagy-nitric oxide reprogramming of immune metabolism: a potential avenue for asthma therapeutic advancement.

Khan Sohrab S, Sammad Abdul A, Madjirebaye Philippe P, Husnain Naqvi Muhammad Ali Ul MAU et al.

Asthma is a complex inflammatory disease where oxidative stress and immune metabolic dysfunction coexist. As master regulators of this interface, macroautophagy/autophagy and nitric oxide (NO) signaling govern immune polarization, metabolic flux, and mitochondrial integrity. While NO functions as a redox messenger that affects both protective and pathogenic outcomes, autophagy maintains cellular homeostasis through coordinated degradation and recycling processes. These pathways come together to form a regulatory triad that controls T-cell differentiation, macrophage activation, and airway remodeling. Here, we outline the ways in which autophagy-NO interactions alter immune metabolism to fuel inflammation in asthma and investigate their potential as a combined therapeutic target. We offer a systems-level perspective of immune reprogramming by mapping important molecular nodes, including those involving MTOR, AMPK, BECN1, NOS2/iNOS, and NOS3/eNOS, and connecting them to metabolic checkpoints. Finally, as a potential avenue that can offer improved efficacy and durability in the management of asthma, we highlight translational strategies that combine autophagy modulators, NO donors or inhibitors, and metabolic regulators.Abbreviations: ASM: airway smooth muscle; COPD: chronic obstructive pulmonary disease; DC: dendritic cell; FAO: fatty acid oxidation; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; L-NIL: L-N6-(1-Iminoethyl)lysine (selective NOS2 inhibitor); M1 and M2: macrophage pro-inflammatory and anti-inflammatory polarization states; NO: nitric oxide; NOS2/iNOS: nitric oxide synthase 2; NOS3/eNOS: nitric oxide synthase 3; OXPHOS: oxidative phosphorylation; PPARGC1A/PGC-1α: PPARG coactivator 1 alpha; ROS: reactive oxygen species; TGFB1/TGF-β1: transforming growth factor beta 1; Treg: regulatory T cell; TSLP: thymic stromal lymphopoietin.

PMID 42504956
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PubMedPhysics in medicine and biology2026-07-27

Quantitative relationship between microdosimetric quantities and plasmid DNA damage induced by auger electrons.

Han Jieun J, Kim Seohan S, Ha Sangseok S, Sung Wonmo W

Objective.This study investigated the microdosimetric characteristics of auger electrons (AEs) and their DNA damage-related physical properties, specifically evaluating the microdosimetric quantity as a physical predictor of initial DNA damage across different radiation types.Approach.Monte Carlo simulations using OpenTOPAS were conducted to calculate the frequency-mean lineal energy (yF) and the dose-mean lineal energy (yD) in spherical water targets (radii: 10-500 nm) for monoenergetic electrons (3-15 keV). DNA damage yields were quantified using TOPAS-nBio with a linear plasmid DNA model. The correlations between microdosimetric quantities and DNA damage were analyzed not only for AEs but also for protons and alpha particles to assess the universality ofyFandyDas potential biological predictors.Main results.AEs demonstrated a pronounced site-radius dependency for bothyFandyDwithin the 10-100 nm target region. Across these biologically relevant nano-scale targets, both strand break (SB) and double-SB (DSB) yields exhibited strong power-law correlations with microdosimetric quantities (R2⩾ 0.94 foryFandR2⩾ 0.89 foryD). Low-energy electrons, protons, and alpha particles aligned along a continuous microdosimetric-damage relationship despite differences in particle identity. Specifically,yFprovided a more sensitive physical predictor thanyDfor Auger electron-induced initial DNA damage in the low-lineal-energy region below 10 keVμm-1.Significance.These findings show thatyFandyDreflect nanoscale energy-deposition patterns governing initial DNA strand-break induction. This microdosimetry-damage relationship extends to low-energy AEs as well as proton and alpha particles.

PMID 42504087
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PubMedAutophagy2026-07-27

Transport of endo-β-mannosidase AtEBM from the cytoplasm to the vacuole through the autophagy pathway in Arabidopsis.

Wei Huan H, Mai Jinyan J, Su Jianyu J, Fang Gengnan G et al.

Macroautophagy/autophagy is a conserved eukaryotic intracellular degradation pathway, with specialized forms such as the biosynthetic cytoplasm-to-vacuole targeting (Cvt) pathway in yeast, which selectively delivers several resident hydrolase precursors to the vacuole rather than for turnover. Although the core autophagy machinery is highly conserved between yeast and plants, whether autophagy plays a biosynthetic role in transporting vacuolar hydrolases in plants has remained unclear. Here, we show that Arabidopsis thaliana AtEBM (endo-β-mannosidase), a glycosidase involved in the degradation of vacuolar N-glycans, is selectively transported to the vacuole via autophagy. Further analyses revealed that AtEBM directly interacts with the core autophagy protein ATG8 through an ATG8-family interacting motif (AIM), and this interaction is essential for sequestering AtEBM into phagophores. Notably, the AIM is conserved among EBM orthologs across the green plant lineage. Phenotypic analyses of CRISPR-Cas9-generated atebm mutants revealed no defects in canonical autophagy markers (such as early senescence and nutrient starvation hypersensitivity); instead, the mutants exhibit reduced fecundity. Collectively, our findings demonstrate that AtEBM is targeted to the vacuole through a selective biosynthetic autophagy, which is functionally similar to, but molecularly distinct from the yeast Cvt pathway.Abbreviations: AIM: ATG8-family interacting motif; Ams1: α-mannosidase; Ape1: aminopeptidase I; ATG: autophagy related; Co-IP: co-immunoprecipitation; ConA: concanamycin A; Prc1/CPY: proteinase C; Cvt cytoplasm‑to‑vacuole targeting; DMSO: dimethyl sulfoxide; EE: early endosome; EBM: endo-β-mannosidase; ER: endoplasmic reticulum; ESCRT: endosomal sorting complexes required for transport; FUC1: α1,3-fucosidase; GFP: green fluorescent protein; GST: glutathione S-transferase; LCI: luciferase complementation imaging; LDS: LIR-docking site; LIR: LC3-interacting region; LUC: luciferase; mAIM: mutated AIM; MS: Murashige and Skoog; MVB: multivesicular body; NBR1: next to BRCA1 gene 1; NVT: NBR1-mediated vacuolar targeting pathway; RFP: red fluorescent protein; TGN: trans-Golgi network; VPE: vacuolar processing enzyme; WT: wild-type; Y2H: yeast two-hybrid.

PMID 42504074
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PubMedProtein & cell2026-07-27

CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence.

Yin Jian J, Gao Yizhou Y, Jing Yaobin Y, Jiang Xiaoyu X et al.

Cellular senescence is accompanied by profound lysosomal alterations, yet whether lysosome-associated factors actively drive aging remains unclear. Through a focused CRISPR/Cas9 screen in human mesenchymal progenitor cells (hMPCs), we identified N-acetylglucosamine-1-phosphotransferase subunits alpha and beta (GNPTAB), an enzyme responsible for lysosomal hydrolase targeting, as a potent regulator of cellular senescence. Genetic ablation of GNPTAB attenuated senescence, whereas its overexpression accelerated senescence. This pro-senescent function occurred independently of GNPTAB's canonical enzymatic role. Instead, GNPTAB binds to the innate immune adaptor stimulator of interferon genes (STING) via a specific interface (E1119), leading to activation of STING and its downstream TANK-binding kinase 1 (TBK1), as well as pro-inflammatory gene expression. A STING-binding-deficient GNPTAB mutant (E1119A) preserved canonical lysosomal functions but failed to induce senescence, while STING depletion abolished GNPTAB-driven senescence. Together, these findings uncover a new signaling pathway wherein GNPTAB engages STING to facilitate its activation, nominating this interface as a potential target for mitigating age-related cellular dysfunction.

PMID 42505080
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