Drug Database
4-

4-factor prothrombin complex

✓ Approved

Intas Pharmaceuticals · F2 · 细胞治疗

什么是 4-factor prothrombin complex?

4-factor prothrombin complex 是一种细胞治疗,由Intas Pharmaceuticals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

公司Intas Pharmaceuticals
药物类别细胞治疗
分子靶点F2, F7, F9, F10
给药途径Injectable (Others), Intravenous (IV)
状态Approved

作用机制

分子靶点

4-factor prothrombin complex 作用于 4 个分子靶点:

F2coagulation factor II, thrombin (THPH1, PT)
F7coagulation factor VII (SPCA)
F9coagulation factor IX (P19, F9 p22)
F10coagulation factor X (FXA, FX)
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

4-factor prothrombin complex 针对 2 个适应症,涉及 1 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersExtravasation blood✓ Approved
Vascular disordersHaemorrhage✓ Approved

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What's New and What's Next for Emicizumab for the Treatment of Hemophilia A?

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Emicizumab, a bispecific factor VIIIa-mimetic antibody, has transformed hemophilia A prophylaxis by providing an effective subcutaneous treatment regardless of factor VIII inhibitor status. The HAVEN program established sustained reductions in treated bleeding, favorable safety, and reduced treatment burden across children and adults. More recent evidence has expanded its use into infancy, previously untreated patients, and selected people with moderate or mild hemophilia A, shifting treatment toward prevention before recurrent bleeding and joint damage occur. Real-world experience broadly confirms the trial's efficacy but also highlights important limitations. Zero treated bleeds does not necessarily indicate absence of pain, synovitis, or progressive arthropathy. At the same time, breakthrough bleeding, laboratory assay interference, rare neutralizing anti-drug antibodies, and thrombotic complications associated principally with excessive activated prothrombin complex concentrate remain clinically relevant. Emicizumab controls bleeding in patients with factor VIII inhibitors but does not induce immune tolerance, leaving unresolved questions regarding inhibitor eradication, delayed factor VIII exposure, and optimal induction of immune tolerance. The next phase of development will require moving beyond uniform weight-based dosing and annualized bleeding rates toward individualized exposure, validated biomarkers, and outcomes that encompass joint structure, physical participation, quality of life, and treatment burden. Emicizumab must also be positioned against next-generation factor VIII mimetics, rebalancing therapies, sustained-exposure factor VIII replacement, and gene therapy. This review critically examines the established and emerging evidence, practical management challenges, unresolved scientific questions, and future therapeutic positioning of emicizumab. Its ultimate impact will depend not only on broader eligibility, but also on precision use, long-term safety, rational treatment sequencing, and equitable global access.

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AKT1-phosphorylated TERT assembles a FOXO3-MYC transcriptional complex that drives ERphagy and proteostasis in post-mitotic RPE.

Babu Vishnu Suresh VS, Ghosh Sayan S, Bammidi Sridhar S, Jiwon Ryu R et al.

The retinal pigment epithelium (RPE) sustains lifelong proteostasis under chronic stress, yet how post-mitotic cells activate macroautophagy/autophagy when canonical kinase pathways suppress it remains unresolved. Here we demonstrate that AKT1 (protein kinase B alpha), drives autophagy through a non-canonical transcriptional mechanism triggered by isoform imbalance. In RPE and age-related macular degeneration (AMD) models, AKT2 (protein kinase B beta) hyperactivation destabilizes MTORC2 (mechanistic target of rapamycin complex 2) and engages RPS6KB/S6K (ribosomal protein S6 kinase beta) -mediated IRS-1 (insulin Receptor Substrate 1) inhibition, creating a feedforward autophagic arrest. Compensatory AKT1 activation via MTORC2 phosphorylates TERT (telomerase reverse transcriptase) at serine 824, driving nuclear translocation that is independent of telomere maintenance. In the nucleus, TERT assembles with FOXO3 (forkhead Box O3) and MYC (MYC proto-oncogene, bHLH transcription factor) into a tripartite transcriptional complex that occupies the EIF2AK3/PERK promoter (eukaryotic translation initiation factor 2-alpha kinase 3/ protein kinase R-like endoplasmic reticulum kinase), enabling EIF2AK3 transcriptional activation. This activity converts the unfolded protein response from pro-apoptotic to cytoprotective: EIF2AK3-ATF4 (activating transcription factor 4) signaling promotes core autophagy machinery biogenesis and selective ERphagy through the receptors TEX264 (testis expressed 264) and CCPG1(cell cycle progression 1), which prevents pathological EIF2AK3 clustering and preserves tubular ER architecture in diseased RPE. Using C. elegans phosphorylation-deficient mutants, mouse models and AMD patient iPSC-RPE, we establish that AKT1-mediated TERT phosphorylation is an evolutionarily conserved prerequisite for FOXO/DAF-16 nuclear function and lysosomal homeostasis in post-mitotic cells, offering therapeutic potential through targeted pharmacologic inhibition of AKT2.Abbreviations: ACTB: actin, beta; AKT1: AKT serine/threonine kinase 1; AKT2: AKT serine/threonine kinase 2; ALP: autophagy-lysosomal pathway; AMD: age-related macular degeneration, ATF4: activating transcription factor 4; ATG3: autophagy related 3; ATG4B: autophagy related 4B cysteine peptidase; ATG7: autophagy related 7; CCPG1: cell cycle progression 1; CFH: complement factor H; C57BL/6J: C57 black 6J; DMSO: dimethyl sulfoxide; MYC: MYC proto-oncogene, bHLH transcription factor; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE-1α: endoplasmic reticulum to nucleus signaling 1; ERphagy: endoplasmic reticulum-selective autophagy; FOXO1: forkhead box O1; FOXO3: forkhead box O3; iPSC-RPE: induced pluripotent stem cell-derived retinal pigment epithelium; ITGB1/integrin β1: integrin subunit beta 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPKAP1/SIN1: MAPK associated protein 1; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2; PBS: phosphate-buffered saline; PI3K: phosphoinositide 3-kinase; RICTOR: RPTOR independent companion of MTOR complex 2; RPE: retinal pigment epithelium; RPTOR: regulatory associated protein of MTOR complex 1; SQSTM1/p62: sequestosome 1; TERT: telomerase reverse transcriptase; TEX264: testis expressed 264, ER-phagy receptor; UPR: unfolded protein response; VCL: vinculin; WT: wild type.

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PubMedTraffic (Copenhagen, Denmark)2026-10-26

TMEM55B Maintains Lysosomal Homeostasis and Promotes ER-Lysosome Calcium Signaling.

Mukae Nagi N, Maki Honoka H, Shirane Michiko M

At membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endolysosomal compartments, the Protrudin-PDZD8 complex promotes the maturation of endosomes into lysosomes, a process accompanied by acidification. Endosomal maturation is closely associated with both lysosomal acidification and calcium signaling; however, the molecular mechanisms linking the Protrudin-PDZD8 complex to these processes remain unclear. Here, we identified TMEM55B, a lysosome-localized protein, as a binding partner of the Protrudin-PDZD8 complex. TMEM55B has been reported to interact with the v-ATPase complex, suggesting a role in lysosomal function. Suppression of TMEM55B expression reduced the fluorescence of a lysosomal acidification probe, suggesting impaired lysosomal acidification. In addition, TMEM55B depletion attenuated lysosomal Ca2+ release and reuptake and reduced ATP-induced Ca2+ responses in the ER. These findings suggest impaired calcium-induced calcium release (CICR) at ER-lysosome MCSs. By contrast, mitochondrial Ca2+ dynamics were unaffected. Together, these results identify TMEM55B as a factor involved in maintaining lysosomal homeostasis and regulating calcium dynamics. Our findings suggest that TMEM55B cooperates with the Protrudin-PDZD8 complex to contribute to the regulation of lysosomal function at ER-lysosome MCSs.

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PubMedBMC pediatrics2026-10-26

Moral distress in pediatric complex care coordinators: a reflexive thematic analysis.

Chahal Simran S, Currie Genevieve G, Ha Seong Eon SE, Kaushik Skanda S et al.

Moral distress can occur in situations where one wants to follow a desired course of action but experiences restraints from internal and external barriers. Unaddressed moral distress is associated with negative outcomes (e.g., burnout). Due to the nature of their work with medically and neurodevelopmentally complex children and their families, pediatrics complex care coordinators are at risk of experiencing moral distress. However, there is limited understanding of moral distress in this professional population. Study objectives were to: (1) understand how pediatric complex care coordinators at a tertiary pediatric hospital defined moral distress; (2) explore factors that influence and modulate moral distress in these care coordinators; and (3) explore the impacts of moral distress on care coordinators. Semi-structured virtual interviews were conducted with twelve pediatric complex care coordinators from a pediatric tertiary care centre to explore experiences with moral distress. Interviews ranged from 25 to 60 min. Interview transcripts were examined by two researchers using inductive reflexive thematic analysis for each objective. The data were analyzed and coded and a 15-point checklist was utilized throughout each phase of the analysis process for consistency amongst coders. All participants reported experiencing moral distress using the seminal definition of moral distress. Care coordinators added additional context and depth to this definition. Factors influencing and modulating moral distress in care coordinators were identified: (1) restrictiveness of their scope and capacity; (2) individual experiences; (3) availability of coping mechanisms; (4) the nature of their interactions; and (5) resolution. Four themes on the impact of moral distress were also identified: (1) changes in perspective; (2) impacts on well-being; (3) need for internal and external change; and (4) influence on interpersonal relationships. An expanded definition of moral distress was co-created with care coordinators and identified factors that influenced moral distress and impacts of moral distress. This work is an important first step to developing a better understanding of moral distress in care coordinators and could inform future interventions to address moral distress in this population.

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PubMedInorganic chemistry2026-10-26

Flexible Transparent Scintillation Films Based on Chiral Molecular Scintillators Showing Strong Circularly Polarized Luminescence and High-Resolution X-ray Imaging.

Tan Li-Hong LH, Yin Si-En SE, Shi Jia-Ran JR, Hu Jun-Jie JJ et al.

Flexible scintillation films based on chiral molecular scintillators have considerable potential for application in advanced technologies, such as three-dimensional displays, optical information storage, and high-resolution diagnostic imaging. Herein, a pair of chiral Cd-Tb complex enantiomers [(R, R)/(S, S)-(L)2TbCd2(H2O)4] (ClO4)3 (R/S -Cd-Tb) was synthesized, and they exhibit a high PLQY of 38.40% and strong circularly polarized luminescence (CPL) with asymmetry factors of 4.69 × 10-2. R/S -Cd-Tb has strong X-ray scintillation performance with a light yield of 2136 and 2111 ph·MeV-1 based on LuAG:Ce and the X-ray detection limit of 50.6 and 52.1 nGy·s-1, respectively. Chiral flexible transparent scintillation films of R/S -Cd-Tb@PMMA were prepared using R/S -Cd-Tb, and the asymmetry factor of the R/S -Cd-Tb@PMMA film is 2.4 × 10-2. The R/S -Cd-Tb@PMMA film exhibits strong circularly polarized radioluminescence (CPRL) and circularly polarized light-emitting diode emission (CP-LEDs). Moreover, it can deliver prominent CPRL signals and achieve high-resolution X-ray imaging with a spatial resolution of 23.96 lp/mm. The results indicate that chiral lanthanide complexes represent a promising class of chiral molecular scintillator materials.

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PubMedInorganic chemistry2026-10-26

Methoxy-Functionalized Coumarin-Sensitized Tris(coumarinate) Sm(III) and Dy(III) Complexes: Tunable Visible and Near-Infrared Luminescence.

Liu Jiaxiang J, Feng Haohao H, Zhou Jianxiong J, Tong Zhongjie Z et al.

Achieving both high photoluminescence quantum yields(ΦLnL) and tunable visible and near-infrared (NIR) emission in organolanthanide (organo-Ln3+) luminophores remains a challenge. Herein, we report a series of ternary tris(coumarinate) Ln3+ complexes, Ln(OMe-Coum)3(2,2'-bpy) (where Ln = La (1), Sm (2), Dy (3), and Gd (4)), by utilizing 4-hydroxy-6-methoxy-3-acetylcoumarin (OMe-Coum) and 2,2'-bipyridine (2,2'-bpy) ligands. Single-crystal X-ray diffraction analysis of the Dy3+ complex reveals a solvent-free mononuclear structure featuring an eight-coordinate {DyO6N2} core with a distorted triangular dodecahedral geometry. The Sm3+ and Dy3+ complexes exhibit dual-mode luminescence, combining residual ligand-centered blue fluorescence with characteristic Ln3+-centered 4f-4f emission. This spectral balance yields purple-pink emission for the Sm3+ complex and near-ideal white-light emission for the Dy3+ analogue, with 1931 Commission Internationale de l'Éclairage coordinates of (0.343, 0.330), a correlated color temperature of 5012 K, and a high color rendering index of 94. Visible-region ΦLnL values are 7% for the Sm3+ complex and 14% for the Dy3+ analogue, with both complexes showing NIR emission. The dual-emissive behavior may arise from incomplete intramolecular intersystem crossing and Ln3+-dependent ligand-to-metal energy transfer efficiency. This work validates methoxy-functionalized coumarin as an efficient sensitizer unit and demonstrates a ternary heteroleptic approach to achieving single-component white-light and NIR luminophores.

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