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asenapine maleate (HP 3070 / HP3070 / Secuado)

✓ Approved

Hisamitsu · DRD1 · 小分子

什么是 asenapine maleate？

asenapine maleate 是一种小分子，由Hisamitsu研发。该药已获批，用于治疗相关适应症，给药途径：Transdermal。

药物档案

商品名HP 3070, HP3070, Secuado
公司Hisamitsu
药物类别小分子
分子靶点DRD1, DRD2, HTR2A
给药途径Transdermal
状态Approved
来源： ClinicalTrials.gov, Hisamitsu

作用机制

分子靶点

asenapine maleate 作用于 3 个分子靶点：

DRD1dopamine receptor D1 (DADR, D1R)
DRD2dopamine receptor D2 (D2DR, D2R)
HTR2A5-hydroxytryptamine receptor 2A (5-HT2A, HTR2)
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

asenapine maleate 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
Psychiatric disordersSchizophrenia✓ Approved
Psychiatric disordersBipolar disorderPhase I

相关研究文献

PubMed[Zhonghua yan ke za zhi] Chinese journal of ophthalmology2026-09-07

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Wang K D KD, Zhao P P, Wu L L LL, Zhang T H TH et al.

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1∶1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80±15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56±3.44) mmHg in the tafluprost/timolol group and (5.36±2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of≥15%,≥25%, and≥30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

PMID 42706141
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PubMedBiochemistry2026-09-03

Fluorine-Induced Elimination Drives Mechanism-Based Inactivation of Isocitrate Lyase.

Fernando Kolambapatabandige Gayantha Shamin KGS, Renault Yohann J G YJG, Molino Rachel R, O'Hagan David D et al.

Fluorinated succinate analogues were evaluated as mechanistic probes of Mycobacterium tuberculosis isocitrate lyase (MtICL). However, 2,2-difluorosuccinate (1; Ki = 6.1 mM) and 2,2,3-trifluorosuccinate (2; Ki = 23.5 μM) act as reversible noncompetitive inhibitors and meso-2,3-difluorosuccinate (3) displayed slow-onset reversible inhibition (Ki = 30 μM), the 2-fluorosuccinate enantiomers ((R)-4 and (S)-4) produced time-dependent irreversible inactivation. Inactivation by 4 was observable under turnover conditions in the presence of glyoxylate and succinate, consistent with a two-step kinetic mechanism. The S enantiomer inactivated more efficiently than (R)-4, consistent with stereoelectronic alignment required for elimination of HF following abstraction of the pro-S proton. 1H NMR analysis detected maleate formation from (S)-4, and mass spectrometry revealed a +132 Da adduct consistent with covalent modification of Cys191. Notably, kinact/KI values for 4 exceeded that measured for maleate, indicating that covalent capture occurs from an enzyme-bound intermediate prior to product release. These results support a mechanism in which fluorine substitution redirects the enolate-generating half-reaction of MtICL toward elimination and covalent modification. (S)-2-Fluorosuccinate therefore represents a succinate-analogue mechanism-based inactivator that exploits a catalytic step distinct from previously described isocitrate-analogue inhibitors.

PMID 42689529
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PubMedJournal of labelled compounds & radiopharmaceuticals2026-09-01

Synthesis and Characterization of 2-(1-Hydroxyethyl)Promazine Sulfoxide-d4 HCl as an Internal Standard for the Accurate Quantitation of 2-(1-Hydroxyethyl)Promazine Sulfoxide in Equine Urine.

Holmes Justin C JC, Smith Ballard C BC, Awuah Samuel G SG, Eisenberg Rodney R et al.

Acetylpromazine, 1-{10-[3-(dimethylamino)propyl]-10H-phenothiazin-2-yl}ethenone, C19H22N2OS, 326.46 g·mol-1 is a phenothiazine derivative at one time used in human medicine as an antipsychotic medication but now predominantly used in veterinary medicine as a sedative/tranquilizer and referred to as acepromazine. In performance horses its use is regulated by using a 10 ng/mL threshold for the major urinary metabolite 2-(1-hydroxyethyl) promazine-sulfoxide (HEPS) in equine urine. To enable accurate quantitation of HEPS in equine urine we have synthesized and purified hydroxyethylpromazine sulfoxide-d4 (HEPS-d4) to be used as a stable isotopically labeled internal standard. Although labeled HEPS is commercially available (CAS 1346605-30-8), to the best of our knowledge there is no published synthetic procedure in the scientific literature. Here we demonstrate a viable synthetic procedure consisting of four major steps: (i) freebasing the Acepromazine maleate salt, (ii) H-D exchange of Acepromazine at room temperature, (iii) reduction of the ketone with NaBD4, and (iv) oxidation of the thioether via hydrogen peroxide and acetic acid. This deuterated internal standard will allow for precise LC/MS quantitation of HEPS at regulatory threshold concentrations, enabling accurate detection and quantitation of picogram/mL concentrations in equine urine samples, thereby supporting regulatory compliance for equine medication control programs.

PMID 42676282
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PubMedPest management science2026-08-28

The I4746K mutation in the ryanodine receptor is associated with high-level resistance to diamide insecticides in Phthorimaea absoluta.

Atış Abdullah Emre AE, Gündüz Kübra Kahveci KK, Yılmazlar Alize A, İnak Emre E et al.

The South American tomato pinworm, Phthorimaea absoluta, has developed resistance to diamide insecticides mainly through target-site mutations in the ryanodine receptor (RyR), including I4746M, G4903E, and G4903V. Recently, a novel mutation, I4746K, has been identified in field populations of P. absoluta, but its contribution to resistance remains unclear. In this study, a field population (TR-Krş-21) harboring the I4746K mutation exhibited 116.65-fold resistance to chlorantraniliprole (CHL). After six rounds of laboratory selection with CHL, resistance increased to 1109.94-fold (CHL-Sel), with a realized heritability of 0.58. Resistance remained stable for 1 year without insecticide exposure, and genetic analyses indicated that it is autosomal, incompletely dominant, and polygenic. Cross-resistance was observed among diamide insecticides, but not to abamectin or broflanilide. Synergist bioassays with piperonyl butoxide and diethyl maleate showed that inhibition of detoxification enzymes did not fully restore susceptibility. CHL selection resulted in a positive correlation between I4746K allele frequency and resistance, and genetic linkage analysis confirmed a significant association between the mutation and the resistant phenotype. Modeling and molecular dynamics simulations revealed that the I4746K substitution reshapes ligand-receptor interactions without markedly reducing overall binding affinity. Finally, a quantitative sequencing protocol and a tetra-primer amplification-refractory mutation system polymerase chain reaction assay were developed for rapid detection of the I4746K mutation. This study emphasizes the significance of the I4746K mutation in diamide resistance and offers valuable insights into how this mutation variably influences the binding of diamide insecticides, thereby informing strategies for resistance management in P. absoluta. © 2026 Society of Chemical Industry.

PMID 42663378
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PubMedInternational journal of molecular sciences2026-08-27

Low-Molecular-Weight Peptides from Musca domestica Larvae Alleviate Diarrhea-Predominant Irritable Bowel Syndrome Comorbid with Depression via Regulating Gut Microbiota, Short-Chain Fatty Acids and Serum Metabolism.

Zhang Xiao X, Jin Xiaobao X, Ma Hongyan H, Chu Fujiang F

Diarrhea-predominant irritable bowel syndrome (IBS-D) frequently occurs alongside depression, greatly impairing patients' life quality, with limited targeted treatments. Low-molecular-weight peptides (LMWPs) from Musca domestica larvae exert gut-protective bioactivities, but their efficacy and molecular mechanisms for comorbid IBS-D and depression remain unelucidated. A chronic-acute combined stress (CACS)-induced rat model of IBS-D complicated with depression was established and treated with LMWPs. The study evaluated intestinal and depressive behavioral phenotypes, and integrated 16S rRNA sequencing, untargeted serum metabolomics and quantitative detection of fecal SCFAs for multi-omics correlation analysis. 1. CACS triggered typical comorbid symptoms, which LMWPs alleviated with effects similar to trimebutine maleate. 2. LMWP treatment was associated with reshaped gut microbiota, restored metabolic pathways, altered levels of 27 disease-associated serum metabolites, and increased fecal SCFA levels. 3. Multi-omics correlation analyses suggested that the therapeutic benefits may involve crosstalk among gut microbiota, SCFAs, and tryptophan metabolites. Larva-derived LMWP relieves IBS-D combined with depression by modulating gut microecology, SCFA generation and serum metabolic balance through the gut-brain axis, which can serve as a novel promising therapeutic candidate.

PMID 42653419
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PubMedJournal of traditional Chinese medicine = Chung i tsa chih ying wen pan2026-08-25

Effects of Biling Weitong granules on gastrointestinal motility and gastrointestinal hormones levels in rats with functional dyspepsia.

Lige Gao G, Xueyi L I LI, Feiyu Chen C, Changyu Jiang J et al.

To investigate the effects of Biling Weitong granules on gastrointestinal motility and serum mouse motilin/human vasoactive intestinal peptide (MTL/VIP) enzyme-linked immunosorbent assay kit levels in functional dyspepsia (FD) rat models, and explore its therapeutic mechanisms against FD to provide further clinical application data. Sixty Sprague-Dawley rats were randomized into blank group (BG) and model group (MG). FD was induced in MG via30-d chronic unpredictable stress. After successful modeling, the model rats were divided into MG BG, Biling Weitong granules low/middle/high-dose (BL/BM/BH), and trimebutine maleate (TM) groups (n = 7/group) for 14-d treatments. At the end of the gavage, General parameters (body weight, food intake), gastrointestinal motility indices (gastric emptying and small intestinal propulsion rates), serum MTL/VIP levels, and gastric antrum histopathology were analyzed using hematoxylin and eosin (HE) staining. After 30 d of modeling, compared with the BG group, rats in the MG group presented FD-like symptoms such as lethargy and irritability, along with significantly decreased body weight and food intake (P < 0.05). The gastric emptying rate and small intestinal propulsion rate were significantly reduced (P < 0.01), and the serum MTL content significantly decreased (P < 0.01). Serum VIP levels were significantly increased (P < 0.01). After 14 d of treatment, compared with the MG group, rats in the BL, BM, BH, and TM groups exhibited improved general condition, with significantly increased body weight and food intake (P < 0.05); significantly faster gastric emptying rate and small intestinal propulsion rate (P < 0.01); and significantly higher serum MTL content (P < 0.01). The serum VIP levels were significantly decreased (P < 0.01). There were no significant differences in body weight or food intake between the BM group and BH group (P > 0.05). Consistently, there were no significant differences in gastric emptying rate, small intestinal propulsion rate, or serum MTL and VIP contents between the BH and TM groups (P > 0.05). HE staining revealed no marked changes in the gastric antrum tissues of the BG, MG, or drug groups. Biling Weitong granules can modulate the levels of the gastrointestinal hormones MTL and VIP in FD rats, promote gastric emptying and small intestinal propulsion, improve the gastrointestinal motility and mental status of FD rats, and alleviate the symptoms of FD, accounting for its efficacy against FD.

PMID 42639771
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