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antithrombin III (Atenotiv / ATenativ / ATnativ)

✓ Approved

Pfizer, Inc. · SERPINC1 · 细胞治疗

什么是 antithrombin III？

antithrombin III 是一种细胞治疗，由Pfizer, Inc.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Atenotiv, ATenativ, ATnativ
公司Pfizer, Inc.
药物类别细胞治疗
分子靶点SERPINC1
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Pfizer, Inc.

作用机制

分子靶点

antithrombin III 作用于 1 个分子靶点：

SERPINC1serpin family C member 1 (ATIII, AT3D)
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

antithrombin III 针对 3 个适应症，涉及 3 个治疗领域。

治疗领域疾病/病症分期
Congenital, familial and genetic disordersAntithrombin III deficiency✓ Approved
Vascular disordersThrombosis✓ Approved
Surgical and medical proceduresAdjuvant therapy✓ Approved

相关研究文献

PubMedFrontiers in pediatrics2026-08-04

Risk factors and a nomogram for predicting severe acute kidney injury in pediatric sepsis: a retrospective study.

Xiang Yiru Y, Zang Ping P, Chen Runfang R, Yan Haipeng H et al.

To develop and validate a nomogram for predicting the risk of severe acute kidney injury (AKI) in children with sepsis. A total of 987 children with sepsis admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital between July 2018 and January 2021 were enrolled. Patients were stratified into a severe AKI group (n = 228) and a no clinically significant AKI group (n = 759) according to the severity of AKI during hospitalization. Based on independent risk factors identified by multivariate logistic regression, a predictive nomogram was constructed. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Severe AKI occurred in 228 patients (23.1%). The mortality rate in the severe AKI group was 2.57-fold higher than that in the no clinically significant AKI group (31.1% vs. 12.5%, P < 0.05). Independent predictors of severe AKI included elevated phosphate (P5+; per 1 mmol/L increase: OR = 2.789, 95% CI = 1.693-4.592, P < 0.001), decreased albumin (ALB; per 1 g/L increase: OR = 0.930, 95% CI = 0.879-0.984, P = 0.012), elevated uric acid (UA; per 1 μmol/L increase: OR = 1.004, 95% CI = 1.003-1.005, P < 0.001), and reduced antithrombin III (AT3; per 1% increase: OR = 0.990, 95% CI = 0.980-0.999, P = 0.048). The logistic regression model showed moderate discrimination with an area under the ROC curve (AUC) of 0.782 (95% CI = 0.744-0.819). The corresponding nomogram achieved an AUC of 0.761 (95% CI = 0.724-0.797). At their optimal cutoff values, the model and nomogram yielded sensitivities of 60.10% and 62.70%, specificities of 85.40% and 80.80%, and Youden indices of 0.455 and 0.435, respectively. Severe AKI is strongly associated with increased mortality in pediatric sepsis. The nomogram incorporating P5+, ALB, UA, and AT3 shows moderate discrimination, acceptable calibration, and potential clinical utility for predicting severe AKI in children with sepsis.

PMID 42548742
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PubMedStatistics in medicine2026-08-04

Conditional Estimations for Seamless Phase II/III Clinical Trials Involving Multi-Stage Early Stopping.

Zhu Siyu S, Yang Yuxuan Y, Yin Minggang M, Luo Yixin Y et al.

To avoid unnecessary resource expenditure resulting from the sample size overestimation in seamless phase II/III designs, multi-stage early stopping may be incorporated in the phase III component. However, existing estimation methods for seamless phase II/III designs are primarily developed for two-stage settings and do not directly accommodate designs with multi-stage early stopping in phase III. In this paper, we develop a Score-statistics-based framework for point and interval estimation in this specific class of designs. The framework provides a design-specific formulation of conditional bias adjustment, conditional median-unbiased estimation, and Rao-Blackwellization for seamless phase II/III designs with multi-stage early stopping. Conditional on the trial continuing to phase III, the proposed framework targets valid and efficient estimation of the treatment effect for the selected arm and is applicable to a range of common endpoint distributions. Within this framework, we formulate and evaluate several representative conditional estimation procedures: the multiple iterations-based conditional bias-adjusted estimator (CBAE-MI), the single iteration-based conditional bias-adjusted estimator (CBAE-SI), the conditional median unbiased estimators with the unselected treatment group effects be estimated by their maximum likelihood estimators (CMUE-MLE) or set as zero (CMUE-ZERO), and the Rao-Blackwellized (RB) estimator. In addition, to properly quantify uncertainty around the point estimates, we derive confidence intervals based on CMUE-MLE, CMUE-ZERO, and RB. Through simulation under various endpoint types and parameter configurations, we recommend employing RB for point estimation and confidence interval, as it demonstrates superior robustness and conservative coverage probability across treatment selection and trial design settings.

PMID 42549628
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PubMedJournal of vascular surgery2026-08-04

A Systematic Review and Meta-Analysis of Prognosis and Revascularization Strategies in Chronic Limb-Threatening Ischemia According to the Global Limb Anatomical Staging System.

Melo Carlos B CB, Pimentel-Junior Dilson D, Obara Mariana K MK, Filippini Denise D et al.

To perform a systematic review and meta-analysis evaluating the prognostic utility of the Global Limb Anatomical Staging System (GLASS) classification in patients with chronic limb-threatening ischemia (CLTI), and to determine which intervention, endovascular or open bypass, is associated with superior outcomes for GLASS III patients. We conducted a systematic review and meta-analysis using PubMed, Scopus, and Cochrane Central from inception through October 2025. Outcomes compared across GLASS stages included immediate technical success (ITS) of endovascular procedures, overall survival (OS), amputation-free survival (AFS), limb salvage (LS), freedom from major adverse limb events (FF-MALE), and limb-based patency (LBP). For patients with GLASS III disease, we directly compared endovascular versus surgical bypass revascularization for OS, FF-MALE, and LS. We included 17 studies in the meta-analysis, comprising 5,290 patients and 5,492 limbs: 945 (17.2%) GLASS I, 1,431 (26.1%) GLASS II, 3,116 (56.7%) GLASS III. Compared with GLASS I, GLASS II presented a significantly higher hazard for LBP failure (HR 1.53; 95% CI 1.06 - 2.20; p = 0.032) and major amputation (endovascular only) (HR 1.45; 95% CI 1.13 - 1.86). When comparing GLASS III to GLASS I, GLASS III had significantly higher hazard for mortality (HR 1.28; 95% CI 1.06 - 1.56; p = 0.021) and MALE (HR 1.36; 95% CI 1.02 - 1.83; p = 0.042), LBP failure (HR 2.23; 95% CI 1.56 - 3.19, p = 0.003). GLASS I presented a significantly higher ITS rate compared to GLASS II (RR 1.03; 95% CI 1.01 - 1.05; p = 0.016) and GLASS III (RR 1.24; 95% CI 1.09 - 1.41; p = 0.005). GLASS II also showed a significantly higher ITS rate compared to GLASS III (RR 1.20; 95% CI 1.04 - 1.38; p = 0.017). No other comparisons across GLASS stages were statistically significant. Among GLASS III patients, we found an increased hazard of MALE in the endovascular group compared to open bypass surgery (HR 1.88; 95% CI 1.35 - 2.61; p = 0.015). No significant differences were identified between endovascular and surgical bypass revascularization for other outcomes. This meta-analysis demonstrates that increasing GLASS anatomical severity is associated with progressively lower ITS following endovascular intervention and increased hazard of LBP failure across all revascularization strategies in patients with CLTI. GLASS I patients, with low complexity anatomies, had a lower mortality and MALE hazard compared with those with high-complexity disease (GLASS III). Among GLASS III patients, endovascular therapy is associated with an increased hazard for MALE compared to bypass surgery.

PMID 42546857
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PubMedDalton transactions (Cambridge, England : 2003)2026-08-04

Ga(III) coordination in peptides viaL-3,4-dihydroxyphenylalanine.

Shang Minghao M, Somathilake Upamali U, Nitsche Christoph C

Bicyclic peptides and gallium are key components of cancer diagnostics as targeting agents and radionuclides, respectively. This study combines both elements without unnatural modifications. Using the natural amino acid L-3,4-dihydroxyphenylalanine (L-DOPA), we create a direct Ga(III)-binding motif in a peptide without compromising biological activity.

PMID 42548178
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PubMedChemistry (Weinheim an der Bergstrasse, Germany)2026-08-04

Synthesis and Structures of Novel Chiral Cyclic Hypervalent Iodine(III) Reagents for Metal-Free Ligand-Transfer Reactions.

Valzer Emmanuel E, Sotiropoulos Jean-Marc JM, Miqueu Karinne K, Pouységu Laurent L et al.

The preparation of novel chiral λ3-iodane reagents bearing transferable halogen-, oxygen- or carbon-based ligands is described. Among these hypervalent iodine(III)-based compounds are (i) the first chiral bis(cyano-λ3-iodane), whose bis(benziodazolone) structure is derived from an enantiopure cyclohexyldiamine-based bis(amidoiodoarene), and (ii) the two first chiral benziodoxolones bearing a carbon-based ligand (i.e., cyano and trifluoromethyl groups) together with a lactate moiety ortho-positioned to the iodine(III) atom. The proposed iodine-containing heterocyclic structures of these new λ3-iodanes are supported by x-ray diffraction analyses and DFT calculations. Their capacity to transfer their ligand(s) in an asymmetric fashion to different substrates (i.e., β-ketoesters, naphthols, and oxindoles) was also examined.

PMID 42549512
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PubMedNucleic acids research2026-08-04

Classification of Sir2-HerA systems reveals a multilayered regulatory cascade gating the type III antiphage activity.

Zhang Xueqi X, Han Jiumin J, Wang Shuangshuang S, Sun Erchao E et al.

Sir2-HerA systems are abortive infection defenses that integrate multiple enzymatic activities to induce growth arrest, thereby limiting phage propagation. However, the molecular logic that couples phage sensing to a precisely gated antiviral response, thereby ensuring infection-specific activation, remains unclear. Through genomic mining of Escherichia coli, we show that E. coli Sir2-HerA immunity diversifies into functional subtypes and identify three types (I-III) with distinct protection profiles. Focusing on the most potent type III system, we identified its phage activators, Gp2.5 and Gp5.9, through an unbiased T7 proteome screen. Mechanistically, type III Sir2-HerA follows a multilayered gating logic. Phage proteins trigger both the HerA nickase and Sir2 NADase; however, the activated NADase remains dormant due to an ATP-mediated checkpoint. The HerA nickase introduces DNA nicks, leading to the accumulation of end-exposed DNA intermediates that engage the complex-associated ATPase to drive ATP consumption. This process relieves the checkpoint, thereby unleashing the full trigger-dependent NADase activity and enabling robust NAD+ depletion. Together, our findings reveal a sophisticated molecular logic that integrates diverse enzymatic activities into a tiered gating architecture, ensuring high-fidelity phage defense while preventing inadvertent activation.

PMID 42549578
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