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tafluprost + timolol maleate (Tapucom / STN 10111 / STN 1011101)

✓ Approved

Santen Pharmaceutical Co., Ltd. · ADRB1 · 小分子

什么是 tafluprost + timolol maleate？

tafluprost + timolol maleate 是一种小分子，由Santen Pharmaceutical Co., Ltd.研发。该药已获批，用于治疗相关适应症，给药途径：Others、Topical。

药物档案

商品名Tapucom, STN 10111, STN 1011101
公司Santen Pharmaceutical Co., Ltd.
药物类别小分子
分子靶点ADRB1, ADRB2, PTGFR
给药途径Others, Topical
状态Approved
来源： ClinicalTrials.gov, Santen Pharmaceutical Co., Ltd.

作用机制

分子靶点

tafluprost + timolol maleate 作用于 3 个分子靶点：

ADRB1adrenoceptor beta 1 (B1AR, RHR)
ADRB2adrenoceptor beta 2 (ADRBR, B2AR)
PTGFRprostaglandin F receptor (FP)
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

tafluprost + timolol maleate 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
Eye disordersGlaucoma✓ Approved

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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PubMedPediatric annals2026-09-03

Recognition and Management of Ulcerative Infantile Hemangioma: Risk Factors, Diagnosis, and Prognosis.

Veronica Elvina E, Cai Qiushuang Q, Shen Qin Q, Jiang Yijing Y et al.

Infantile hemangioma (IH) is a benign tumor that appears in the first year of life and typically involutes within 3 to 4 years. Ulcerative IH, the most common complication, poses a significant burden to patients. Early referral of high-risk cases reduces morbidity. Current literature on risk factors and prognosis is limited. Segmental and mixed IH in urogenital, head, neck, and lip areas show higher ulceration risk. Diagnosis is typically clinical; histopathology is rarely performed. Atypical cases require positive glucose transporter-1 immunohistochemistry. Larger lesions, delayed intervention, and bacterial infection worsen prognosis, prolong healing, and increase recurrence. Condition-dependent treatments, including oral propranolol (starting at 1 mg/kg or less daily, maintenance at 2 to 3 mg/kg daily), timolol prophylaxis, and wound management care combined with laser therapy, shorten therapy duration and minimize recurrence. Empiric antibiotics are indicated for infected ulcerative IH. Surgery is indicated for life-threatening cases (eg, chest wall hemangiomas requiring transfusion or airway obstruction) and high-morbidity cases (eg, lip lesions affecting speech or periorbital lesions impairing vision). The Infantile Hemangioma Referral Score helps clinicians identify high-risk patients who require prompt referral, thereby preventing delayed treatment.

PMID 42692987
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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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PubMedGenes2026-08-27

Exploratory Analysis of Glaucoma-Associated SNPs in a Colombian Cohort Highlights Potential Involvement of Oxidative, Vascular, and Neurodegenerative Pathways.

Casanova Carlos C, Valencia-Peña Claudia C, Saldarriaga-Gil Wilmar W, Lozano-Cruz Edgar E et al.

Primary open-angle glaucoma (POAG) is a complex multifactorial optic neuropathy involving genetic, vascular, oxidative, inflammatory, and neurodegenerative mechanisms. Despite advances in genome-wide studies, the contribution of genetic variants remains incompletely characterized in underrepresented Latin American populations. This study aimed to characterize the genetic landscape of POAG in a Colombian cohort by identifying previously reported glaucoma-associated variants, rare candidate variants, and pharmacogenomic markers and integrating these findings into biologically relevant pathways. An exploratory descriptive study was conducted in 21 Colombian patients with confirmed POAG. Whole-exome sequencing (WES) was performed at an average sequencing depth of approximately 100×. Variants were quality-filtered, functionally annotated, and prioritized within 446 POAG-associated genes retrieved from DisGeNET. Previously reported glaucoma-associated variants and rare candidate variants were identified, while pharmacogenomic variants related to latanoprost and timolol response were evaluated using ClinPGx/PharmGKB. Identified genes were classified according to major biological pathways relevant to glaucoma pathophysiology. Of the 446 POAG-associated genes, 381 were detected in the patients' exomes. A total of 10,220 molecular variants were identified, of which 1,187 synonymous variants were excluded, leaving 9,033 variants for downstream analysis. Among these, 955 were non-synonymous SNVs, including 26 variants previously reported in association with glaucoma and 929 potentially novel coding variants. Previously reported variants included loci in SIX6, LOXL1, CYP1B1, NOS3, and SOD2. Two rare candidate variants (minor allele frequency <1%) were identified in FMNL2 and C3. Pharmacogenomic variants in PTGS1, ADRB1, and ABCC4 with potential implications for response to latanoprost or timolol were also detected. Functional integration highlighted pathways involving oxidative stress, extracellular matrix remodeling, vascular regulation, neurodegeneration, and inflammation. This exploratory analysis identifies known glaucoma-associated variants, rare candidate variants, and pharmacogenomic markers in Colombian patients with POAG. The findings support a multifactorial biological framework involving interconnected oxidative, structural, vascular, neurodegenerative, and inflammatory pathways. The FMNL2 and C3 variants represent candidates for further investigation, while the identified pharmacogenomic variants highlight the potential relevance of genomic profiling for personalized glaucoma management. Larger ancestry-informed case-control studies are required to validate these observations and determine their clinical significance.

PMID 42650112
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