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4-

4-factor prothrombin complex

✓ Approved

Intas Pharmaceuticals · F2 · Cell-based Therapies

What is 4-factor prothrombin complex?

4-factor prothrombin complex is a cell-based therapies developed by Intas Pharmaceuticals. It is approved for therapeutic indications via injectable (others) or intravenous (iv).

Drug Profile

CompanyIntas Pharmaceuticals
Drug ClassCell-based Therapies
Molecular TargetF2, F7, F9, F10
RouteInjectable (Others), Intravenous (IV)
StatusApproved
Sources: ClinicalTrials.gov, Intas Pharmaceuticals

Mechanism of Action

Molecular Targets

4-factor prothrombin complex acts on 4 molecular targets:

F2coagulation factor II, thrombin (THPH1, PT)
F7coagulation factor VII (SPCA)
F9coagulation factor IX (P19, F9 p22)
F10coagulation factor X (FXA, FX)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

4-factor prothrombin complex is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersExtravasation blood✓ Approved
Vascular disordersHaemorrhage✓ Approved

Related Research Articles

PubMedNature plants2026-08-25

Plant-specific and conserved mechanisms of the polymerase-associated factor 1 complex in replication stress responses.

Li Cunliang C, Guo Yuyu Y, Wang Ziying Z, Zheng Haowei H et al.

DNA replication stress threatens genome stability, but how plants respond to this challenge remains unclear. Here we show that the evolutionarily conserved polymerase-associated factor 1 complex (PAF1C) is required for the replication stress response in Arabidopsis. Plants lacking functional PAF1C are hypersensitive to replication stress-inducing agents. Mechanistically, we reveal a plant-specific pathway in which the stress-activated kinase WEE1 phosphorylates PAF1 to prevent its protein degradation, a regulatory mechanism absent in yeast. By contrast, we uncover a conserved pathway in which the replication factor C (RFC) complex recruits PAF1C to stalled replication forks, where PAF1C in turn recruits the E2 ubiquitin-conjugating enzymes UBC1/2 and the E3 ubiquitin ligases HUB1/2 to promote histone H2B monoubiquitination, thereby stabilizing the forks. Collectively, our findings suggest that PAF1 regulates replication stress responses by integrating a plant-specific protein stability control mechanism (WEE1-PAF1) with a conserved recruitment mechanism (RFC-PAF1-UBC1/2-HUB1/2). This work establishes a new function for PAF1C and expands the mechanistic understanding of WEE1 and the RFC complex in the replication stress response.

PMID 42637853
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PubMedLab on a chip2026-08-25

Design and development of a smart, intuitive and cost-efficient paper-based platform for whole blood PT/INR diagnostics.

Saha Anubhuti A, Bajpai Ashutosh A, Shukla Praveen P, Verma Rakesh R et al.

Frequent monitoring of prothrombin time and international normalized ratio (PT/INR) is essential for effective management of anticoagulation therapy, yet conventional laboratory-based testing remains costly, time-consuming, and difficult to access in decentralized settings. Addressing this challenge, a hybrid paper-based point-of-care (POC) platform is designed for rapid and affordable whole-blood PT/INR analysis. The assay is developed through systematic optimization of key parameters, including sample volume, blood-to-reagent ratio, reaction time, substrate type, assay geometry, and strip dimensions for both haematocrit (HCT) and PT/INR modules. The integrated system simultaneously estimates HCT using radial intensity-based detection on Whatman Grade 4 paper (R2 = 0.9788) and measures PT/INR on high-porosity MF1 glass-fibre strips (R2 ≈ 0.94), enabling correction of HCT-induced bias. Image-derived features were analyzed using AI/ML-based models, where support vector machine classifiers achieved diagnostic accuracies of 98.5% and 96.9% for non-anticoagulated and anticoagulated cohorts, respectively. Integrated with a custom desktop/web/smartphone application and an automated warfarin dosage calculator, the platform provides a low-cost, rapid, and user-friendly solution for accessible anticoagulation monitoring.

PMID 42638485
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PubMedFrontiers in cardiovascular medicine2026-08-25

Prediction of mortality risk in patients with peripheral artery disease using interpretable machine learning.

Li Yifei Y, Zhang Qiang Q, Zhao Wenxin W, Sun Qingyuan Q et al.

Patients with peripheral artery disease (PAD) face high postoperative mortality risks, necessitating precise risk stratification. While machine learning offers superior performance, its black-box nature limits clinical utility, and the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) remains controversial. A total of 610 surgically managed PAD patients were enrolled (median follow-up: 4 years) and randomly split into training (70%) and test (30%) sets. Six machine learning algorithms were constructed and optimized. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The sHapley additive exPlanations (SHAP) were employed for model interpretation and visualizing nonlinear relationships. The random forest model achieved optimal performance (test set AUC = 0.814) with significant clinical net benefit. SHAP analysis identified age, prothrombin activity, and Rutherford classification as top predictors. Notably, while multivariate Cox regression failed to identify NLR as a linear predictor, SHAP dependence plots revealed a distinct nonlinear pattern: risk contribution increased sharply at low standardized NLR values before plateauing. We established an interpretable random forest model for predicting postoperative mortality in PAD. By integrating SHAP analysis, this study validates the nonlinear prognostic significance of NLR and demonstrates how explainable ML can complement traditional statistics for individualized risk assessment.

PMID 42638675
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PubMedFrontiers in tuberculosis2026-08-25

Sigma factor M induces an ESX-4-focused regulon in Mycobacterium abscessus.

Canestrari Jill G JG, Gianola Shawn S, Derbyshire Keith M KM, Gray Todd A TA

Mycobacteria encode as many as five distinct Type VII (ESX) secretion systems that function in nutrient acquisition, cell-cell interaction, membrane integrity and pathogenesis. The biological activities of ESX systems are determined by the effector proteins they secrete. ESX-4 is the ancestral secretion system and is conserved throughout mycobacteria, including Mycobacterium abscessus where it has been shown to support survival in phagosomes. ESX-4 and putative effector genes in Mycobacterium tuberculosis and Mycobacterium smegmatis are co-induced by a conserved sigma factor, SigM. Identifying the activities conferred by ESX-4 in promoting M. abscessus survival begins with identifying potential secreted substrates. We hypothesized that, in M. abscessus, SigM co-regulates the expression of genes encoding ESX-4 components and secreted effector proteins. We generated a precise deletion of the sigM-rsmA locus, encoding SigM and its dedicated anti-sigma factor. Performing RNA-seq using this deletion strain and a SigM-expressing complementation derivative, we identified SigM-responsive mRNAs in M. abscessus. Analysis of responsive promoters defined a consensus SigM-binding site, indicating direct induction by SigM. Together these data defined 15 SigM-targeted loci transcribing 50 genes with annotations and structures consistent with ESX secretion. While SigM induces multiple esx4 locus promoters in M. smegmatis, only the promoter encoding the primary EsxU/EsxT secreted substrates are direct targets in M. abscessus, suggesting that production of the secretion apparatus is controlled by other transcription factors. The putative effector complexes identified here present strong candidates for the pathogenic roles previously reported for ESX-4 in M. abscessus infection models.

PMID 42638806
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PubMedAngewandte Chemie (International ed. in English)2026-08-25

A Cytochrome P450 Enzyme-Catalyzed Acetyl Migration in Cyanogramide Biosynthesis.

Zhu Yiguang Y, Wang Yongchao Y, Zhang Liping L, Fang Chunyan C et al.

Cyanogramide (1) is a unique spirooxindole alkaloid derived from a marine actinomycete and is characterized by its distinct spirocyclic pyrrolo[1,2-c]imidazolidin-4-one scaffold. Although we have successfully elucidated the biosynthetic pathway of 1, the mechanism underlying the formation of the characteristic imidazolidin-4-one remains unclear. In this study, we demonstrate that the cytochrome P450 monooxygenase CyaI catalyzes an oxidation reaction through a zwitterionic intermediate and facilitates a subsequent unusual C→N acetyl migration, which triggers a spontaneous intramolecular cyclization to forge the imidazolidin-4-one ring during 1 biosynthesis. In addition, CyaI is identified as a bifunctional enzyme that also catalyzes N-demethylation. High-resolution crystallography and mutagenesis studies determine Thr245 as a crucial catalytic residue that modulates the balance between imidazolidine-4-one synthesis and demethylation. This work not only expands the catalytic repertoire of P450 enzymes but also opens the way for the development of multifunctional biocatalysts in the synthesis of complex natural products.

PMID 42638169
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PubMedJournal of traditional Chinese medicine = Chung i tsa chih ying wen pan2026-08-25

Jianchang No. 1 (1) formula alleviates irritable bowel syndrome with diarrhea improving gut microbiota and regulating toll-like receptors/nuclear factor-kappa B signaling pathway in bowel syndrome with diarrhea rats.

Yutong Liu L, Yan Yang Y, Huiying X U XU, Lei L I LI et al.

To evaluate the therapeutic efficacy of Jianchang No. 1 (1) in treating irritable bowel syndrome with diarrhea (IBS-D) and to explore its underlying mechanisms of action. IBS-D rat models were established through a combination of chronic restraint stress, water avoidance stress, and the administration of senna decoction. Body weight, fecal water content (FWC), and intestinal capacity threshold in IBS-D rats were monitored before and after treatment. Pathological alterations in colon tissue were examined using hematoxylin and eosin staining. Serum levels of lipopolysaccharide (LPS), along with LPS content in colon tissue were measured using the enzyme-linked immunosorbent assay. 16S rRNA sequencing technology was employed to assess the abundance and compositional shifts within the gut microbiota. Quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence were employed to determine gene and protein expression in colonic samples. Jianchang No. 1 treatment restored body weight, lowered FWC, and raised the intestinal capacity threshold in IBS-D rats. Meanwhile, Jianchang No. 1 enhanced both the richness and composition of the gut microbiota. Moreover, Jianchang No. 1 markedly upregulated the tight-junction proteins zonula occludens-1 and occludin together with the anti-inflammatory cytokine interleukin-10, while simultaneously downregulating the LPS-toll-like receptor (TLR) 2/4- myeloid differentiation factor 88- nuclear factor kappa B (NF-κB) axis and the downstream pro-inflammatory mediators interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, together with interleukin-4 and interferon-gamma. Jianchang No. 1 maintains intestinal barrier integrity by reshaping gut-microbial diversity and composition, dampening the TLR/NF-κB signaling cascade, and thereby alleviating low-grade colonic inflammation and its attendant clinical symptoms in IBS-D rats.

PMID 42639773
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