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celecoxib + tramadol HCl (MR308 / Velyntra / Seglentis)

✓ Approved

Kowa · OPRM1 · 小分子

什么是 celecoxib + tramadol HCl？

celecoxib + tramadol HCl 是一种小分子，由Kowa研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名MR308, Velyntra, Seglentis
公司Kowa
药物类别小分子
分子靶点OPRM1, PTGS2, SLC6A2, SLC6A4
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Kowa

作用机制

分子靶点

celecoxib + tramadol HCl 作用于 4 个分子靶点：

OPRM1opioid receptor mu 1 (MOP, M-OR-1)
PTGS2prostaglandin-endoperoxide synthase 2 (PHS-2, PGG/HS)
SLC6A2solute carrier family 6 member 2 (NAT1, NET)
SLC6A4solute carrier family 6 member 4 (SERT1, 5-HTTLPR)
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

celecoxib + tramadol HCl 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Gastrointestinal disordersAbdominal pain✓ Approved
Injury, poisoning and procedural complicationsProcedural painPhase III

相关研究文献

PubMedDiabetes, obesity & metabolism2026-09-10

Dose-Normalised Time in Range (dn-TIR) Improves Following Hybrid Closed-Loop (HCL) Therapy in Type 1 Diabetes: A Real-World Cohort Study From Australia and the United Kingdom.

Wellens-Mensah Jude J, Konantambigi Akash A, Lopez Keimee K, Triay Jessica J et al.

To evaluate dose-normalised time in range (dn-TIR) and its log relative change (Δdn-TIR) as measures of within-person glycaemic change relative to total daily insulin exposure following hybrid closed-loop therapy (HCL/AID). We conducted a retrospective two-cohort study of people with type 1 diabetes commencing hybrid closed-loop/automated insulin delivery (HCL/AID) therapy in Australia and the United Kingdom (UK). dn-TIR was calculated as time in range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) divided by total daily insulin dose (TDD) and Δdn-TIR as log[(TIR/TDD)post/(TIR/TDD)pre]. The study comprised 86 people living with type 1 diabetes in Australia and 288 in the UK. In the fixed Australian dn-TIR cohort, TIR increased from 53.2% ± 20.7% to 70.4% ± 14.6% (n = 86; p < 0.001), whereas mean TDD changed from 53.3 to 52.0 units/day (n = 86; p = 0.724). Median Δdn-TIR was 0.224 [IQR: -0.033, 0.583]. In the UK cohort, TIR increased from a median 54% [34, 68] to 66% [54, 74] (n = 257; p < 0.001), whereas mean TDD changed from 44.1 to 46.3 units/day (n = 242; p = 0.152). Median Δdn-TIR was 0.194 [IQR: -0.097, 0.541]. HCL/AID therapy improved TIR relative to TDD in two real-world cohorts. dn-TIR and Δdn-TIR are not replacements for established CGM metrics or direct measures of insulin sensitivity; they may provide an adjunct longitudinal description of whether glycaemic improvement was accompanied by proportionately greater, similar or lower insulin exposure.

PMID 42717560
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PubMedJournal of medicinal chemistry2026-09-10

From Fragment Hit to Clinical Candidate: Discovery of Dual H1R/H4R Ligands with Superior Efficacy in Allergic Conjunctivitis.

Weber Peter P, Smits Rogier R, Lim Herman D HD, Andaloussi Mounir M et al.

Dual inhibition of the histamine H1 and H4 receptors (H1R and H4R) has been shown to provide superior anti-inflammatory efficacy in preclinical models of allergic disease compared to selective inhibition of either receptor alone. Building on this concept, we initiated a fragment-based discovery program and previously identified a quinazoline-containing fragment hit. Here, we describe the lead optimization toward compounds with unique dual H1R/H4R activity. Structure-activity relationship studies yielded potent and balanced ligands with nanomolar affinities for both receptors, as well as pharmacokinetic properties suitable for ocular administration. Among these, quinazoline 35.HCl (GD136) and tetrahydroquinazoline 72.HCl (GD134) demonstrate robust in vivo efficacy in a ragweed-induced mouse model of allergic conjunctivitis, significantly reducing hyperemia and outperforming selective H1R or H4R antagonists. Based on its pharmacological profile, ADME properties, ease of formulation, and in vivo efficacy, GD134 was selected as the clinical development candidate for a first-in-class dual-targeted therapy of allergic conjunctivitis.

PMID 42720497
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PubMedJournal of the International Society of Sports Nutrition2026-09-10

Creatine formulations and repeated sprint training: effects on physical and physiological adaptations in soccer players during the short-term preparation phase.

Duan Changyuan C, Wang Zaitao Z, Wang Qianjin Q

This research examined the impact of various creatine (Cr) supplementation formulations during a 4-week preparatory phase on the efficacy of repeated sprint training (RST) and on improvements in physical and physiological performance in male soccer athletes. A total of forty collegiate young soccer players volunteered for the study. They were randomly divided into four groups: creatine monohydrate (Cr-Mon, n = 10), creatine ethyl ester (Cr-Ee, n = 10), creatine hydrochloride (Cr-Hcl, n = 10), and placebo (PL, n = 10). All athletes engaged in a 4-week training intervention, three times a week (i.e. 12 sessions), and physical (countermovement vertical jump [CMVJ], 20-m sprint, and L-run) and physiological (Wingate anaerobic power and incremental exercise tests) performance were assessed both before and after the training period. All training groups improved physical and physiological performance following the 4-week intervention period (p < 0.05). Additionally, the groups receiving the Cr supplement exhibited significantly greater changes (p = 0.001) in physical performance, peak power output, and fatigue index compared to the PL group. However, no significant differences were found among the groups regarding mean power output and VO2max. Notably, the Ee and Hcl forms of Cr showed superior gains (p < 0.05) in physical performance and peak power compared to the Mon form after the 4-week intervention. The results underscore the importance of Cr ingestion in enhancing adaptations for short-term physical performance tasks, highlighting the effectiveness of the Ee and Hcl forms in further improving the CMVJ, 20-m sprint, L-run, and peak power among soccer players during the short-term preparation phase.

PMID 42720250
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PubMedRSC advances2026-09-10

Tailored [1,2,4]triazolo[1,5-a]pyrimidine hybrids as promising anti-inflammatory agents with COX/5-LOX/ROS/IL-6 multifunctional inhibitory activity: design, synthesis, SAR, and in silico study.

Elazony Esraa E, Osman Nermine A NA, Shaldam Moataz A MA, Abdel-Fattah Hanan A HA et al.

To develop potent anti-inflammatory agents with safer profiles, a hybridization approach combining [1,2,4]triazolo[1,5-a]pyrimidine/chalcone (5a-g) and [1,2,4]triazolo[1,5-a]pyrimidine/pyrazole (6a-g) has been rationally designed to synthesize potential COX/5-LOX/ROS/IL-6 multifunctional inhibitors. All synthesized hybrids were evaluated in vitro using biological COX-1/COX-2 assays. Compounds 5a, 6c, and 6d displayed the highest COX-2 potency and selectivity (5a; IC50 = 1.361 µM, SI = 12.86, 6c; IC50 = 2.537 µM, SI = 18.05, and 6d; IC50 = 1.237 µM, SI = 8.917), outperforming the reference diclofenac sodium (IC50 = 4.812 µM, SI = 2.552). These promising derivatives were selected for further in vitro assays to evaluate their inhibitory effects on 5-LOX, ROS, and IL-6. The most potent COX-2 inhibitor 6d exhibited reasonable 5-LOX inhibitory activity (IC50 = 1.031 µM) in comparison to the selective 5-LOX inhibitor zileuton (IC50 = 0.386 µM). Moreover, 6d exhibited potent inhibitory activity against the proinflammatory cytokine IL-6 (90.9% inhibition) and ROS scavenging activity (IC50 = 34.45 µM), exceeding the two references, celecoxib and diclofenac sodium. Furthermore, compound 6c displayed substantial inhibition of TNF-α release (69.44%), approaching that of the reference drug diclofenac sodium (75.75%). Ultimately, docking simulations and drug-likeness studies provided insights into the potential binding scenarios within the active sites of COX-2 and 5-LOX, while also predicting the oral bioavailability and toxicity of the newly synthesized compounds. Based on these findings, the designed scaffolds can be considered as promising multitargeted anti-inflammatory candidates worthy of further exploration.

PMID 42719759
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PubMedRheumatology (Oxford, England)2026-09-09

Celecoxib plus topical flurbiprofen patch versus celecoxib alone for symptomatic knee osteoarthritis: a randomized controlled trial.

Sun Kaibo K, Pu Min M, Zhang Huaixian H, Bai Liangtao L et al.

Rapid symptom control may facilitate earlier mobility and self-management in symptomatic knee osteoarthritis (KOA), but evidence for combining oral and topical non-steroidal anti-inflammatory drugs (NSAIDs) remains limited. This study aimed to determine whether adding a topical flurbiprofen patch to oral celecoxib provides greater short-term improvements in pain, physical function, quality of life, and patient global assessment than oral celecoxib alone in patients with symptomatic KOA. In this open-label randomized controlled trial conducted at a tertiary academic hospital from January 2024 to March 2025, 90 patients with chronic inflammatory symptomatic KOA were randomized 1:1 to receive either oral celecoxib 200 mg once daily or celecoxib plus topical flurbiprofen patch twice daily. Outcomes were assessed at baseline and on days 3, 7, and 14. Primary outcomes were pain severity by visual analog scale (VAS) and functional impairment by WOMAC. Secondary outcomes included quality of life by SF-36 and patient global assessment (PGA). Eighty-nine patients completed the study (45 celecoxib; 44 combination therapy). Baseline characteristics were comparable between groups. Compared with celecoxib alone, combination therapy produced greater early pain relief, with larger VAS reductions on day 3 (3.4 ± 0.9 vs. 2.0 ± 0.8, p < 0.01) and day 7 (3.9 ± 1.0 vs. 3.3 ± 1.0, p = 0.02), but not day 14. WOMAC improvement was greater in the combination group on days 3, 7, and 14 (all p < 0.01). At day 14, SF-36 health domain scores and PGA ratings were also higher with combination therapy. Adding topical flurbiprofen patch to oral celecoxib provided faster early improvement in pain and function and better short-term patient-reported outcomes in symptomatic KOA. Chinese Clinical Trial Registry: ChiCTR1800014584.

PMID 42714961
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PubMedThe Journal of chemical physics2026-09-09

Dynamically biased microcanonical treatment of HCl dissociative chemisorption on Au(111) yields thermal associative desorption dynamics by detailed balance.

Bernard Mark E ME, Harrison Ian I

A dynamically biased microcanonical transition state theory model of HCl dissociative chemisorption on Au(111) was recently developed for Shirhatti et al.'s [J. Phys. Chem. Lett. 7, 1346 (2016)] non-equilibrium supersonic molecular beam experiments where normal translational energies varied over a 50-250 kJ/mol range. Model parameters include a relatively low threshold energy for reaction, E0 = 30.88 kJ/mol; an efficiency, εn = 0.26, for molecular normal translational energy to contribute to the active exchangeable energy capable of promoting reaction; and one surface oscillator, s = 1, involved in the local gas-surface collision complex wherein energy was taken as microcanonically exchangeable, although potentially subject to dynamical bias through efficiencies. To validate the model, detailed balance was used to predict the desorbing HCl product state distributions from thermal associative desorption of H(c) + Cl(c) on Au(111) that have been measured by Rettner and Auerbach [Science 263, 365 (1994)] while impinging a H atom beam onto a chlorinated Au(111) surface. Modeling of Rettner's [J. Chem. Phys. 101, 1529 (1994)] rovibrationally resolved HCl product state distributions allowed for the additional establishment of a rotational efficiency of εr = 0.23 that led to consistent prediction of both the thermal associative desorption and the supersonic molecular beam experimental results. The HCl(g) ⇄ H(c) + Cl(c) reactivity on Au(111) is thereby identified as a new benchmark system for gas-surface reactivity where highly detailed experimental data are available coming from both sides of the reaction barrier. The activation energy for thermal associative desorption was estimated as Ea,assoc = 5.6 ± 1.3 kJ/mol based on four independent kinds of measurement. The effect of dynamics on the thermal dissociative sticking coefficient, S(T), of interest in practical catalysis, was quantitatively assessed. As compared to a statistically behaving HCl/Au(111) system with Ea = 31 kJ/mol, dynamics reduced S(T) by a factor of 10 at 800 K, equivalent to an increase in activation energy of ΔEa = 15 kJ/mol.

PMID 42713950
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