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dihydroergotamine mesylate (INP104 / I104 / Trudhesa)

✓ Approved

Impel Pharmaceuticals Inc · HTR1D · Small Molecule

What is dihydroergotamine mesylate?

dihydroergotamine mesylate is a small molecule developed by Impel Pharmaceuticals Inc. It is approved for therapeutic indications via inhaled or intranasal.

Drug Profile

Brand NamesINP104, I104, Trudhesa
CompanyImpel Pharmaceuticals Inc
Drug ClassSmall Molecule
Molecular TargetHTR1D
RouteInhaled, Intranasal
StatusApproved
Sources: ClinicalTrials.gov, Impel Pharmaceuticals Inc

Mechanism of Action

Molecular Targets

dihydroergotamine mesylate acts on 1 molecular target:

HTR1D5-hydroxytryptamine receptor 1D (HTR1DA, HT1DA)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

dihydroergotamine mesylate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersMigraine✓ Approved

Related Research Articles

PubMedThe American journal of case reports2026-11-11

Primary Synovial Sarcoma of the Thyroid Gland Presenting With Early Pulmonary Metastasis: Diagnostic Pathway, SS18 Gene Fusion Confirmation, and Clinical Course.

Edwards Andrew G AG, Petroski Jack J, Patel Raj R, Koyfman Sergey S

BACKGROUND Primary synovial sarcoma of the thyroid gland (PSST) is an exceptionally rare and aggressive neoplasm. Twenty-one cases have been reported in the literature to date, making this the 22nd reported occurrence. This report presents the case of a 47-year-old woman with PSST confirmed by SS18 gene fusion on fluorescence in situ hybridization (FISH), who subsequently developed pulmonary metastasis and doxorubicin-induced congestive heart failure, illustrating the aggressive clinical course of this entity. CASE REPORT We report the case of a 47-year-old woman presenting with dysphagia and a left-sided neck mass. Initial FNA was non-diagnostic; repeat FNA raised concern for a spindle cell neoplasm. Left hemithyroidectomy was performed with negative margins, and SS18 gene fusion was confirmed by FISH, establishing the diagnosis of PSST. Following multidisciplinary review, adjuvant chemotherapy was deferred and neck radiation was administered. Pulmonary metastasis was discovered 6 months postoperatively. The patient received eribulin mesylate and subsequent palliative doxorubicin, and her case was complicated by doxorubicin-induced congestive heart failure. She subsequently developed progressive systemic metastatic disease, including brain and bone involvement, and died of the disease 65 months after initial presentation. CONCLUSIONS This case demonstrates that SS18 FISH confirmation is essential when FNA is non-diagnostic for a thyroid spindle cell mass. Despite negative margins and adjuvant radiation, early pulmonary metastasis and ultimately fatal systemic metastatic disease to the brain and bone occurred, underscoring the aggressive clinical course of PSST. Doxorubicin-induced cardiac toxicity further illustrates the systemic therapy burden. BCL-2-directed strategies remain investigational. Complete surgical resection with negative margins is the cornerstone of management.

PMID 43010634
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PubMedPLoS pathogens2026-11-10

Modulation of Fe3+ homeostasis by African Swine Fever virus facilitates its efficient replication in Ornithodoros lahorensis and pigs.

Sun Hua-Lin HL, Liu Ying Y, Hao Rong-Zeng RZ, Zhao Zi-Min ZM et al.

African swine fever virus (ASFV) can be transmitted through direct contact and, in specific ecological settings, by Ornithodoros spp. soft ticks. However, the cellular mechanisms that support ASFV replication in both porcine host and tick vector remain poorly understood. Iron is essential for cellular metabolism and viral replication, but excessive labile iron can induce oxidative stress and ferroptosis-like morphological changes in mitochondria. Whether and how ASFV exploits intracellular Fe3+ homeostasis to sustain its replication has not been fully defined. In this study, proteomic analysis of ASFV-infected PAM (pig) and OME/CTVM24 (derived from Ornithodoros moubata) cells revealed a marked reduction in ferritin/FTH1 abundance, suggesting that ASFV infection alters intracellular iron storage and availability. Further analyses showed that ASFV dynamically regulated labile Fe3+ levels during infection. At the early stage, ASFV promoted NCOA4-associated ferritin turnover, increased labile Fe3+ release, enhanced mitochondria-endoplasmic reticulum contact, and induced ferroptosis-like changes in mitochondrial morphology. At later stages, ASFV restrained excessive iron-associated damage, thereby maintaining an intracellular environment compatible with continued viral replication. Pharmacological depletion of labile iron with deferoxamine mesylate markedly suppressed ASFV replication in both porcine and tick-derived cells, indicating that controlled Fe3+ availability is required for efficient viral propagation. Mechanistically, the ASFV-encoded protein pA151R interacted with NCOA4 and promoted autophagic degradation of FTH1 in a manner dependent on its intact LC3-interacting region motif. pA151R also impaired mitochondrial outer membrane integrity and disrupted MDA5-MAVS/VISA signaling. Deletion of A151R impaired the ability of ASFV to modulate Fe3+ homeostasis and significantly reduced viral replication. ASFV infection increased serum iron levels in pigs and caused abnormal iron redistribution and depletion in splenic tissues in vivo. Similar iron depletion and transient ferroptosis-like morphological changes in mitochondria were observed in the salivary glands of ASFV-infected O. lahorensis. Collectively, these findings demonstrate that ASFV exploits Fe3+ homeostasis through a pA151R-NCOA4-FTH1-dependent mechanism to support replication in host and vector cells. This study provides new insights into ASFV metabolic regulation and identifies iron homeostasis and pA151R-mediated ferritinophagy as potential targets for strategies aimed at limiting ASFV replication and tick-associated transmission.

PMID 43008086
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PubMedSpectrochimica acta. Part A, Molecular and biomolecular spectroscopy2026-11-08

Seed-mediated synthesis of Au@Ag core-shell nanoparticles as SERS substrates for rapid identification and quantification of four quinolone antibiotic residues in aquatic samples.

Zhang Ziwen Z, Wu Dongan D, Liang Ping P, Li Jinru J et al.

Antibiotic residues in aquaculture threaten food safety and ecological balance, calling for rapid and sensitive analytical methods. Herein, uniform Au@Ag core-shell nanoparticles (Au@Ag NPs) were fabricated via a seed-mediated strategy and used as SERS substrates for the sensitive detection and spectral discrimination of four quinolone antibiotics: enrofloxacin, enoxacin, levofloxacin, and danofloxacin mesylate. Using malachite green (MG) as a probe, the substrate showed an ultra-low LOD of 8.17 × 10-14 M and an enhancement factor of 1.64 × 108. Good batch-to-batch reproducibility (RSD = 5.75%), signal uniformity (RSD < 7.5%), and 60-day stability (69.60% residual signal) were achieved. Individual quantitative detection of the four antibiotics gave LODs ranging from 0.00031 to 0.0049 ppm. On grass carp scales as a complex aquatic matrix, concentration-dependent SERS signals and good linear calibration curves were obtained. Recovery experiments gave recoveries of 83.14%-116.61%, with RSD values below 9.5%, indicating satisfactory analytical accuracy and repeatability. PCA was employed for spectral dimensionality reduction to distinguish the four structurally similar quinolones. The first three principal components accounted for 86.5% of the total variance and achieved complete separation in 2D and 3D score plots. Overall, this study of four representative quinolones under controlled exposure conditions provides a foundation for further evaluation of matrix variability, competitive adsorption in mixed-residue systems, and performance in naturally contaminated samples, while demonstrating the potential of the Au@Ag NP-based SERS platform combined with chemometric classification for rapid screening of quinolone residues in aquaculture applications.

PMID 42998499
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PubMedFrontiers in immunology2026-11-05

Eribulin mesylate in combination with ivonescimab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer(EMIT): study protocol for a single-arm, multicenter clinical trial.

Lu Haiqi H, Wang Xufei X, Wang Zhuo Z, Chen Miaoqin M et al.

Advanced triple-negative breast cancer (TNBC) has an extremely poor prognosis, and current therapies offer limited benefits for patients with low programmed cell death ligand 1(PD-L1) expression. This study innovatively proposes a "novel chemotherapy + bispecific antibody" model. Eribulin Mesylate (hereinafter referred to as Eribulin), a novel microtubule inhibitor, kills tumor cells while remodeling the tumor microenvironment. When combined with the PD-1/VEGF bispecific antibody Ivonescimab, it concurrently dismantles immunosuppression and angiogenesis to synergistically overcome immunotherapy resistance. This is a multicenter, open-label, single-arm clinical trial designed to enroll 29 patients with locally advanced or metastatic TNBC who have not received prior systemic anticancer therapy, and who are either ineligible for radical surgical resection or local therapy, or have experienced disease progression following postoperative adjuvant therapy. The primary endpoint is the objective response rate (ORR) assessed by Investigator Assessment (INV) at each participating center based on strict adherence to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1) criteria. Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Exploratory endpoints involve potential biomarkers, the correlation between PD-L1 expression and efficacy, and patient-reported outcomes (PROs). This combination regimen is expected to leverage the synergistic advantages of "chemotherapy-promoted immunity and potent bispecific antibody efficacy," providing novel evidence-based medical evidence for the first-line treatment of metastatic TNBC and thereby effectively addressing significant unmet clinical needs. http://www.chictr.org.cn/, identifier ChiCTR2600117652.

PMID 42984708
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PubMedFrontiers in pharmacology2026-11-05

Successful application of low-dose regional citrate combined with nafamostat mixed anticoagulation in CRRT for patients with liver failure: a retrospective case series study of 11 patients.

Zhang Yanting Y, Ma Jing J, Xiao Le L, Ye Jian J et al.

To investigate the clinical efficacy, safety and operational feasibility of a low-dose regional citrate anticoagulation (RCA) combined with low-dose nafamostat mesylate (NM) mixed anticoagulation regimen in continuous renal replacement therapy (CRRT) for patients with liver failure, so as to provide clinical reference for the selection of CRRT anticoagulation strategies for such special high-risk critically ill patients. A retrospective case series study was conducted. Eleven patients with liver failure who received CRRT in the Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University were enrolled. All patients were treated with CVVHDF mode and uniformly implemented the low-dose citrate combined with nafamostat mixed anticoagulation regimen. CRRT treatment parameters, anticoagulant drugs, and infusion doses of calcium and sodium bicarbonate were standardized. The monitoring frequency of peripheral blood gas and activated partial thromboplastin time (APTT) and the criteria for dose stratification adjustment were standardized. Data including patients' demographic baseline data, CRRT treatment duration, filter service life, blood gas electrolytes, dynamic changes of APTT, pipeline and filter coagulation, bleeding and metabolic adverse events, organ function and clinical outcomes were collected for summary and analysis. A total of 11 patients with liver failure undergoing CRRT in CVVHDF mode were enrolled in this study, using the low-dose regional citrate combined with nafamostat mixed anticoagulation regimen. After treatment, the median filter life of patients reached 48 (38, 68.75) hours, with no severe pipeline or filter coagulation; there were no significant abnormalities in systemic coagulation indicators. One case (9.1%) had mild oral mucosal bleeding; no severe massive bleeding occurred. Hypocalcemia and metabolic alkalosis were observed in several patients but were not severe, and no citrate accumulation, severe hypocalcemia, or severe acid-base or electrolyte disorders occurred. PCT was lower than baseline (P = 0.005) and APACHE II score was improved (P = 0.011) over the course of ICU treatment; however, all patients simultaneously received antibiotics, vasopressors, source control, and other ICU supportive care, and these changes therefore cannot be attributed to the mixed anticoagulation regimen. Liver and kidney function showed no obvious deterioration. In this small, single-center retrospective case series, a low-dose regional citrate combined with nafamostat mixed anticoagulation regimen was feasible to implement in patients with liver failure receiving CRRT. In this cohort, the median filter life was 48 h, no severe filter or pipeline coagulation was observed, and no citrate accumulation, severe hypocalcemia, or severe acid-base or electrolyte disorders occurred; one case (9.1%) had mild bleeding. Because no comparator group was included, whether these observations reflect a benefit of the mixed regimen over conventional RCA, nafamostat alone, systemic heparin, or no anticoagulation cannot be determined. These findings are preliminary and hypothesis-generating and require confirmation in adequately powered, multicenter, prospective controlled trials.

PMID 42984532
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PubMedCell biology and toxicology2026-11-03

Hepatitis B virus X protein stabilizes TPM1 to epigenetically inhibit ALDH2 and drive liver cancer progression.

Kong Fanyun F, Wang Yuxin Y, Yang Lu L, Jiang Rong R et al.

As a major viral oncogenic factor, the hepatitis B virus (HBV) X protein (HBx) critically contributes to the malignant progression of liver cancer (LC). Although cytoskeletal proteins are implicated in HBx-mediated tumorigenesis, their specific functions and underlying mechanisms in HBx-associated LC remain largely underexplored. Here, we identified that tropomyosin 1 (TPM1), an actin-binding cytoskeletal protein, is significantly overexpressed in HBx-positive LC cells and HBV-associated tumor tissues. Both in vitro and in vivo experiments demonstrated that TPM1 contributes to HBx-induced growth and migration of LC cells. Furthermore, HBx can stabilize TPM1 by disrupting its interaction with SYVN1, an E3 ubiquitin ligase. Additionally, aldehyde dehydrogenase 2 (ALDH2) was identified as a key downstream effector of TPM1. TPM1 markedly downregulates ALDH2 expression, leading to cholesterol accumulation. Specifically, TPM1 binds to histone deacetylase 2 (HDAC2), an epigenetic coregulator, and represses ALDH2 transcription by reducing histone acetylation at the ALDH2 promoter region. Interestingly, HBx enhances the interaction of TPM1with HDAC2, resulting in greater downregulation of ALDH2. Through high-throughput virtual screening and experimental validation, dihydroergotamine mesylate was further identified as a specific TPM1 inhibitor. This compound exerted potent antitumor effects by counteracting HBx-induced cholesterol accumulation and oncogenic phenotypes in LC cells. Collectively, these results delineate a mechanism by which the cytoskeletal protein TPM1 facilitates HBx-induced hepatocarcinogenesis and highlight TPM1 as a promising therapeutic target for HBV-positive LC. suppressing histone acetylation. DHE, a newly identified inhibitor of TPM1, restrains HBx-mediated LC cell biological behaviors.

PMID 42975690
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