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dihydroergotamine mesylate (INP104 / I104 / Trudhesa)

✓ Approved

Impel Pharmaceuticals Inc · HTR1D · 小分子

什么是 dihydroergotamine mesylate？

dihydroergotamine mesylate 是一种小分子，由Impel Pharmaceuticals Inc研发。该药已获批，用于治疗相关适应症，给药途径：Inhaled、Intranasal。

药物档案

商品名INP104, I104, Trudhesa
公司Impel Pharmaceuticals Inc
药物类别小分子
分子靶点HTR1D
给药途径Inhaled, Intranasal
状态Approved
来源： ClinicalTrials.gov, Impel Pharmaceuticals Inc

作用机制

分子靶点

dihydroergotamine mesylate 作用于 1 个分子靶点：

HTR1D5-hydroxytryptamine receptor 1D (HTR1DA, HT1DA)
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

dihydroergotamine mesylate 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
Nervous system disordersMigraine✓ Approved

相关研究文献

PubMedFrontiers in bioinformatics2026-10-27

Identification and validation of biomarkers related to oxidative stress in pediatric sepsis utilizing WGCNA and multiple machine learning algorithms.

Liu Yumeng Y, Luo Gang G

This research aimed to identify novel oxidative stress (OS)-related biomarkers and develop predictive models for the early detection of pediatric sepsis. Five open-access datasets from the gene expression omnibus database were analyzed, which included peripheral whole blood samples from children with sepsis and healthy controls. Using bioinformatics approaches, we identified differentially expressed genes (DEGs) associated with OS. We then combined weighted gene co-expression network analysis (WGCNA) and multiple machine learning algorithms (ML) to identify seven candidate genes, constructed a protein-protein interaction (PPI) network to screen six hub genes, and evaluated their correlations with the immune microenvironment. We subsequently evaluated the diagnostic performance of the hub genes using training datasets (GSE26440 and GSE26378) and validation datasets (GSE13904, GSE8121, and GSE9692). Moreover, molecular docking analysis revealed interactions between hub gene-encoded proteins and small-molecule compounds, which helps predict drug sensitivity. The study identified 36 differentially expressed oxidative stress-related genes (OSRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted these genes' roles in regulating inflammatory responses and reactive oxygen species metabolism. Seven candidate genes were identified using machine learning algorithms. Subsequently, through protein-protein interaction (PPI) network analysis, six hub genes, namely, GADD45A, HP, MAPK14, PGD, RETN, and S100A9, were identified as having significant diagnostic potential. Immune cell deconvolution analysis of peripheral blood transcriptomes suggested that hub genes related to oxidative stress may be linked to alterations in the composition of peripheral blood immune cells. The diagnostic performance of the six hub genes was validated with area under the curve (AUC) values between 0.908 and 0.982, showing their promising diagnostic performance. Additionally, molecular docking analysis suggested that small molecules Doxycycline, Ralimetinib mesylate, Tasquinimod might interact with the identified hub genes, which opens up new treatment options. Our research not only reveals potential diagnostic biomarkers of pediatric sepsis but also sets the stage for future studies. These studies aim to translate our findings into clinical practice, enabling earlier and more accurate diagnoses as well as targeted therapies to improve outcomes for children.

PMID 42935671
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PubMedThe protein journal2026-10-25

Interactions of Veterinary Antibiotics with Purified Bovine Milk Alkaline Phosphatase: A Combined In Vitro Kinetic and Theoretical DFT/HF/M06-2X Study.

Bilen Çiğdem Ç, Tüzün Burak B, Gencer Nahit N

Alkaline phosphatase (AP, EC 3.1.3.1) is a key metalloenzyme and has been widely used as a reliable marker for milk pasteurization. Milk containing antibiotic residues tends to inhibit AP function, which can result in faulty pasteurization determination. AP from bovine milk was purified by a purification strategy involving butanol homogenization, rennet precipitation, and Sephadex G-100 gel filtration chromatography. The enzyme was purified 53.43-fold with a specific activity of 7516.40 EU/mg. Kinetic characterization showed a KM value of 2.27 mM (Vmax value: 555.56 EU/min); substrate was p-nitrophenyl phosphate. Electrophoretic studies verified the purity and molecular nature of the product enzyme. To functionally validate the identity of the purified enzyme, tetramisole hydrochloride was evaluated as a standard reference inhibitor, yielding a potent IC₅₀ value of 0.045 mM. Fifteen veterinary drugs and antibiotics were used to test the inhibitory effects of purified milk AP in vitro. Among the antibiotic compounds tested, Danofloxacin Mesylate induced the strongest antibiotic inhibition (IC50: 3.36 mM). Gentamycin Sulfate, Metamizole Sodium, Enrofloxacin, Kanamycin Sulfate, Sulfadimidine Sodium, and Neomycin Sulfate had IC50 values ranging between 22.89 and 312.13 mM of inhibition in AP, while Dexamethasone, Oxytetracycline Hydrochloride, Marbofloxacin, Tilmicosin, Doxycycline Monohydrate, Tylosin, Florfenicol and Flunixin Meglumine made no detected inhibition in the presence of 0.5 mM p-nitrophenyl phosphate. The molecular docking studies were additionally performed that the density functional theory (DFT), Hartree-Fock (HF), and M06-2X calculations were used to validate the experimental results with the 6-31++G(d,p) basis set. The theoretical results also reported that Oxytetracycline Hydrochloride, Tilmicosin, and Doxycycline Monohydrate displayed superior electronic reactivity, lower energy gaps between HOMO-LUMO, and more electrophilic character compared with the other compounds. These results are the first complete assessment of the impact of veterinary antibiotics in milk AP and underscore the possible role of antibiotic residues in establishing the reliability of pasteurization control measures.

PMID 42927595
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PubMedMacromolecular rapid communications2026-10-22

Protic Poly(Diallylammonium Sulfonate)s: Toward Water-Processable Fluorine-Free Ionic Materials.

Pairetti Yuliana Y, Rolandi Ana Clara AC, Casado Nerea N, Forsyth Maria M et al.

In this work, we report the synthesis of a new family of fluorine-free protic poly(ionic liquid)s via free-radical cyclopolymerization of protic diallylammonium monomers. Protic ionic liquid monomers based on diallylmethylammonium (DAMAH+) and diallylammonium (DAAH2 +), combined with different alkyl sulfonate counter-anions, were first prepared. Cyclopolymerization yielded a systematic series of six poly(diallylammonium) cations, five of which are newly reported here, combining two polymer backbones-poly(DAMAH+) and the newly incorporated poly(DAAH2 +)-with three fluorine-free sulfonate anions, namely mesylate (MsO-), ethylsulfonate (EsO-), and dodecylbenzenesulfonate (DBsO-); the previously reported poly(DAMAH+MsO-) analogue was included for direct comparison within the same series. Systematic characterization reveals how the interplay between polymer backbone and counter-anion governs solubility in water and organic solvents, glass transition temperatures (20-55°C), thermal stability (up to 300°C), and ionic conductivity (up to 10-3 S cm-1 at 100°C). The combination of their physicochemical properties, electrochemical stability, and water processability highlights these polymers as a versatile fluorine-free platform for electrochemical technologies. To demonstrate this potential, selected polymers were evaluated as water-processable binders for LiFePO4 cathodes, where they delivered competitive rate capability and stable electrode performance compared to PVDF. Their protic ionic character further suggests opportunities for future applications toward proton-conducting materials. Overall, this work introduces a sustainable platform for the development of fluorine-free ionic polymers with broad potential for electrochemical technologies.

PMID 42904760
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PubMedAnti-cancer agents in medicinal chemistry2026-10-19

Imatinib-Based Derivative: Synthesis, Computational Modeling, and Experimental Anticancer Activity.

Saidov Ravshan R, Gulyamov Shokhid S, Elmurodov Laziz L, Makhkamov Mukhriddin M et al.

Cancer remains one of the major causes of death worldwide. Tyrosine kinase inhibitors (TKIs) represent an important class of targeted anticancer agents because they block key oncogenic signaling pathways. Imatinib mesylate was among the first TKIs introduced in clinical oncology and has significantly improved the treatment of several malignancies. Nevertheless, its clinical use is associated with adverse effects, which highlights the need to develop modified derivatives with improved efficacy and reduced toxicity. In the present work, a new compound, imatinib aescinate, was prepared by dissolving imatinib and aescin separately in ethyl alcohol and combining the solutions under continuous stirring, followed by filtration and acetone-induced precipitation. For identification and structural characterization, the compound was analyzed using UV and FTIR spectroscopy, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), thermogravimetric-differential thermal analysis (TGA/DTA), and HPLC. Antiproliferative activity was assessed in MCF-7 breast cancer cells using a CCK-8 cell viability assay (24 h), and wound closure was evaluated using a scratch assay. To understand potential molecular interactions, molecular dynamics simulations together with MM-PBSA binding energy calculations were also performed. The synthesized compound exhibited greater antiproliferative activity against MCF-7 cells than either imatinib mesylate or aescin alone. The IC50 values determined from a 24 h CCK-8 assay were: imatinib aescinate 15.16 μM, aescin alone 23.55 μM, and imatinib mesylate 76.66 μM. Imatinib aescinate also inhibited MCF-7 wound closure in a concentration-dependent manner in the scratch assay. Computational analysis indicated stable binding of imatinib aescinate to the BCR-ABL tyrosine kinase (PDB ID: 2HYY). Molecular dynamics simulations suggested reduced conformational flexibility of the protein-ligand complex, and MM-PBSA calculations supported favorable binding energy. Imatinib aescinate was approximately fivefold more potent than imatinib mesylate and 1.6-fold more potent than aescin, indicating enhanced antiproliferative activity. Its concentration-dependent inhibition of wound closure also suggests potential antimigratory effects, although reduced cell proliferation may contribute to this result. Computational findings supported stable and favorable binding to BCR-ABL; however, the underlying mechanism requires experimental confirmation. Further studies should evaluate kinase inhibition, toxicity, and in vivo efficacy. Overall, the results indicate that imatinib aescinate shows enhanced antiproliferative activity against MCF-7 cells compared with its individual components. Computational predictions suggest that the compound may interact with kinase targets; however, direct biochemical validation is required before definitive mechanistic conclusions can be drawn. These findings identify imatinib aescinate as a promising candidate for further preclinical investigation as a potential anticancer agent.

PMID 42895164
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PubMedMolecules (Basel, Switzerland)2026-10-16

Coffee Husk-Derived Activated Carbon for the Adsorptive Removal of Imatinib Mesylate from Water: Kinetic, Isotherm, Thermodynamic, and DFT Studies.

Párraga-García Vivian V, Chiquito Jeniffer J, Montero-Calderón Carolina C, Manangon-Perugachi Lucia E LE et al.

Coffee husk-derived activated carbon prepared by H3PO4 chemical activation was investigated for the removal of imatinib mesylate from aqueous solutions. Structural and chemical characterization using N2 physisorption, SEM, FTIR, Raman spectroscopy, and thermogravimetric analysis revealed a porous carbon matrix containing oxygenated functional groups and a defective turbostratic structure. The adsorption behavior was evaluated through batch experiments by examining the effects of pH, adsorbent dosage, particle size, contact time, and initial drug concentration. Under optimized conditions (300 µm particle size, 0.6 g adsorbent dosage, and pH 6), imatinib mesylate removal reached 97.9%, with equilibrium achieved within 60 min. The adsorption kinetics followed the pseudo-second-order model (R2 = 0.946-0.984), while equilibrium data were best described by the Sips isotherm model (R2 > 0.99), indicating adsorption on a heterogeneous surface. Density functional theory calculations confirmed the contribution of oxygen-containing groups, with carboxyl-functionalized carbon exhibiting the strongest interaction with imatinib mesylate (-105.3 kJ mol-1). These findings highlight the potential of coffee husk-derived activated carbon as a sustainable adsorbent for pharmaceutical contaminant removal.

PMID 42883159
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PubMedNeuroscience2026-10-09

Concurrent salivation and lacrimation after superior and inferior salivatory nuclei glutamate/NMDA receptor excitation in the rat.

Ramos Juan M J JMJ

Recently it has been suggested that the somas of the lacrimal nucleus and salivatory nuclei are, to a certain extent, anatomically intermingled all along the parvocellular reticular formation. The objective of this study was to investigate, using a physiological approach, the topographical relationship between salivatory and lacrimal cells. To this end the cell bodies of the superior (SSN) and inferior (ISN) salivatory nuclei were activated following a microinjection of NMDA. Results showed that NMDA administered to the SSN produced an increased secretion of submandibular-sublingual saliva, but not parotid saliva, concurrently with lacrimation. On the other hand, NMDA administered to the ISN produced hypersecretion of parotid, but not submandibular-sublingual saliva, concurrently with lacrimation. These secretory effects were blocked by i.p. administration of atropine but not when dihydroergotamine plus propranolol was administered, which points to the parasympathetic nature of the activated cells. Although the diffusion of the NMDA has not been evaluated directly, and it is not possible to pinpoint the anatomical specificity of the microinjections, these findings do suggest, from a functional perspective, the coexistence of salivatory and lacrimal cells in the same regions, or regions very close to one another, in the brainstem.

PMID 42854777
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