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metoprolol ER + hydrochlorothiazide (Selopress Zok / Dutoprol)

✓ Approved

AstraZeneca UK Limited · ADRB1 · Small Molecule

What is metoprolol ER + hydrochlorothiazide?

metoprolol ER + hydrochlorothiazide is a small molecule developed by AstraZeneca UK Limited. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesSelopress Zok, Dutoprol
CompanyAstraZeneca UK Limited
Drug ClassSmall Molecule
Molecular TargetADRB1
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, AstraZeneca UK Limited

Mechanism of Action

Molecular Targets

metoprolol ER + hydrochlorothiazide acts on 1 molecular target:

ADRB1adrenoceptor beta 1 (B1AR, RHR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

metoprolol ER + hydrochlorothiazide is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedMolecular oncology2026-07-17

Pharmacological chromatin remodeling enhances response to estrogen therapy in ER+ breast cancer.

Johnson Thomas Anneka L AL, Karakyriakou Barbara B, Muskus Patricia C PC, Roberts Alyssa M AM et al.

Estrogen therapy elicits clinical benefit in ~ 30% of patients with endocrine-resistant estrogen receptor (ER)-positive breast cancer, but its mechanism of action and strategies to increase efficacy remain unclear. Estrogen therapy can induce ER transcriptional hyperactivation and DNA damage; we postulated that such damage could be exacerbated by epigenetic dysregulation via inhibition of histone deacetylases (HDACi). We evaluated the effects of 17b-estradiol and HDACi in three types of ER+ breast cancer models: Cells adapted to growth following long-term estrogen deprivation; cells engineered to overexpress exogenous ER that confers endocrine resistance; mice bearing endocrine-resistant patient-derived xenografts. Assay endpoints included apoptosis, growth, DNA damage, histone post-translational modification, levels of ER-regulated transcripts and encoded proteins, cell cycle and replication status, and genome-wide chromatin accessibility, ER binding, and transcriptional profiles. Entinostat treatment increased histone acetylation and chromatin accessibility. Combination treatment with E2 and entinostat inhibited cell growth and induced apoptosis in ER-overexpressing models. E2 and entinostat induced DNA damage as single agents and in combination. These agents synergized against tumor models, offering HDACi as a strategy to enhance efficacy of estrogen therapy.

PMID 42464636
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PubMedPlant-environment interactions (Hoboken, N.J.)2026-07-17

Enhanced Endogenous GABA Biosynthesis Modifies Fruit Production and GABA Accumulation in a Medium-Sized Tomato Cultivar Under Salt Stress.

Suzuki Toon T, Takayama Mariko M, Ezura Hiroshi H

While exogenous γ-aminobutyric acid (GABA) enhances plant stress tolerance, fruit responses to increased endogenous GABA biosynthesis remain unclear. Although high-GABA traits mitigate productivity loss in cherry tomatoes under salt stress, salinity responses differ among cultivars, and whether this occurs in medium-sized tomatoes remains unknown. We tested whether endogenous GABA enrichment maintains production and promotes dry matter and GABA accumulation under salt stress. The medium-sized tomato 'Esprosso' (ER), and its genome-edited high-GABA line (ERHG) were grown under control and salt stress conditions. Under salt stress, fruit fresh weight decreased by 43.4% in ER and 31.5% in ERHG, whereas fruit number per plant increased by 33.3% in ER and 71.1% in ERHG. Due to this compensatory increase, mean yield changes (+2.6% in ER and +11.1% in ERHG) were not statistically significant. Dry matter content increased by 0.6 percentage points (pp) in ER and 1.5 pp. in ERHG, showing a significant genotype × salt stress interaction. Salt stress elevated GABA concentration by 64.5% in ER and 74.4% in ERHG (from 141.5 to 246.8 mg 100 g-1 FW), increasing per-fruit GABA content by 22.8% in ERHG. Total soluble solids (TSS) and ascorbic acid increased under salt stress in both genotypes, indicating the high-GABA trait did not reduce TSS, whereas proline showed a genotype-dependent response. These results suggest that enhanced endogenous GABA biosynthesis modifies fruit responses to salt stress by promoting GABA and dry matter accumulation and altering osmolyte-related metabolism without reducing TSS, potentially contributing to high-value tomato production under controlled salinity.

PMID 42465054
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PubMedScience bulletin2026-07-17

Biallelic hexose-6-phosphate dehydrogenase variants cause mitochondrial dysfunction underlying Parkinson's disease.

Zhao Miao M, Zhao Yuwen Y, Huang Juan J, Guo Yu Y et al.

Parkinson's disease (PD) is a progressive neurodegenerative disorder influenced by complex genetic and environmental factors. We report that biallelic variants in hexose-6-phosphate dehydrogenase (H6PD), which encodes a key enzyme in the endoplasmic reticulum (ER) pentose phosphate pathway, contribute to PD and investigate its role in maintaining mitochondrial homeostasis. Through whole-exome sequencing of 2223 patients with PD and 1229 controls, together with whole-genome sequencing of 4010 patients and 6072 controls, we found 13 biallelic H6PD variants in eight probands, including two homozygous and six compound heterozygous cases (six early-onset PD, two late-onset PD). Functional studies were conducted using cultured cells, Drosophila, and AAV-shRNA-mediated H6PD knockdown mice. Mitochondrial function and redox status were assessed using confocal imaging, flow cytometry, and Seahorse metabolic flux analysis. ER-mitochondria contacts, Ca2⁺ dynamics, and mitophagy were evaluated using SPLICS sensors, calcium imaging, and PINK1-Parkin pathway assays. Our study revealed that H6PD depletion impaired NADPH generation, disrupted ER-mitochondria coupling, caused abnormal Ca2+ release, mitochondrial fragmentation, reduced respiratory capacity, and suppressed PINK1-Parkin-dependent mitophagy. PD-related H6PD variants lost the ability to maintain NADPH/redox balance and mitochondrial protective function. In Drosophila, H6PD loss induced dopaminergic neurodegeneration, locomotor deficits, and shortened lifespan, all partially rescued by human H6PD. Similarly, H6PD knockdown in mice aggravated MPTP-induced neuronal loss and mitochondrial abnormalities. In conclusion, our study identifies biallelic variants in H6PD as a novel cause of PD. H6PD maintains ER NADPH/redox homeostasis, stabilizes ER-mitochondria communication, and preserves mitochondrial function and mitophagy, thereby supporting dopaminergic neuron survival.

PMID 42463407
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PubMedAllergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology2026-07-17

Comparative effectiveness of mepolizumab and omalizumab in patients eligible for both: a retrospective cohort study.

Nagai Tatsuya T, Inoshima Naoki N, Matsui Hiroki H, Kubota Norihiko N et al.

Omalizumab and mepolizumab are effective biologic therapies for severe asthma. However, their comparative effectiveness in patients eligible for both treatments remains unclear in routine care. Therefore, the aim of this study was to compare the real-world effectiveness of mepolizumab and omalizumab in these patients. This retrospective cohort study included patients with asthma who were treated with omalizumab or mepolizumab. Eligible patients had a blood eosinophil count ≥ 150 cells/μL (or ≥ 300 cells/μL within the prior year), total Immunoglobulin E (IgE) ≥ 30 IU/mL, and sensitization to a perennial inhalant allergen. The primary endpoint was the adjusted incidence rate ratios (IRRs) for asthma exacerbation during the first year of treatment. Secondary endpoints were IRRs for emergency room (ER) visits and hospitalizations, subgroup IRRs stratified by baseline eosinophil count (< 300 cells/μL vs. ≥ 300 cells/μL), and change in oral corticosteroid (OCS) dose. Poisson regression models were adjusted for BMI, eosinophil count, and prior-year exacerbations; ER and hospitalization models additionally adjusted for prior ER visits and hospitalizations. Follow-up time was accounted for via an offset term. We included 49 patients (omalizumab, n = 25; mepolizumab, n = 24). Mepolizumab significantly reduced asthma exacerbations compared with omalizumab (IRR, 0.37; 95% confidence interval [CI], 0.19-0.69). In the subgroup analyses, this effect was significant in patients with baseline eosinophil counts < 300 cells/μL (IRR, 0.38; 95% CI 0.14-0.88) but not in those with baseline eosinophil counts ≥ 300 cells/μL (IRR, 0.47; 95% CI 0.15-1.35). There were no significant between-group differences in the number of ER visits or hospitalizations. The OCS dose was reduced in both groups, with no significant between-group difference in the mean dose reduction. In patients eligible for both therapies, mepolizumab reduced clinically significant exacerbations more than omalizumab in real-world practice. Although ER visits, hospitalizations, and OCS-sparing were comparable, these findings may help inform biologic selection when exacerbation reduction is prioritized but require confirmation in larger multicenter studies.

PMID 42464416
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PubMedbioRxiv : the preprint server for biology2026-07-17

VESTA: Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features.

Trisha Simina Mannan SM, Rahman Md Ashiqur MA, Hassan Md Walid MW, Gi Young Jin YJ et al.

Viscoelastic characterization of tissue has significant diagnostic value in oncology, as tumor progression alters both elasticity and viscosity in ways that neither property alone can fully capture. Existing acoustic radiation force (ARF)-based methods such as Viscoelastic Response (VisR) ultrasound estimate relative elasticity and viscosity through per-A-line nonlinear model fitting, which is computationally intensive and requires auxiliary simulations to correct elasticity-dependent bias. This work presents VESTA (Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features), a two-stage data-driven pipeline that predicts elasticity ratio (ER) and viscosity ratio (VR) directly from seven normalized ARFI displacement features at the A-line level, without model fitting or compensation. Stage 1 is an MLP classifier that detects inclusion boundaries from normalized peak displacement and negative peak velocity ratios; Stage 2 is a dilated Conv1D regression model that estimates ER and VR along the full axial sequence using the predicted mask alongside displacement features. The pipeline was trained on 500 simulated inclusion scenarios spanning three geometries, five focal depths, two F-numbers, and a broad range of material contrasts. In silico, mean predicted ER and VR were within 12% of ground truth across all geometries, with performance best when ER and VR were moderate or decoupled. Experimental validation on a chicken breast phantom demonstrated plausible generalization to real tissue heterogeneity. Applied to an in vivo murine 4T1 breast cancer model, the pipeline tracked treatment-related attenuation of mechanical contrast in paclitaxel-treated tumors relative to controls over a 36-day imaging period, supporting its relevance for tumor monitoring.

PMID 42465280
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PubMedFrontiers in medicine2026-07-17

Efficacy of acupuncture combined with exercise rehabilitation on cardiac function in patients with heart failure: a systematic review and meta-analysis.

Hu Jiale J, Du Hongsen H, Chen Ting T, Hu Yuanhui Y et al.

Exercise rehabilitation (ER) is recommended in both national and international guidelines for heart failure (HF). However, patients with severe symptoms may derive limited benefit from ER alone. Acupuncture has shown potential cardioprotective and symptom-relieving effects in some clinical studies, suggesting that acupuncture combined with exercise rehabilitation (ACER) may be a promising adjunctive strategy. This systematic review aimed to compare the efficacy of ACER with that of ER alone in patients with HF. The Cochrane Library, PubMed, Ovid, Wanfang Medical Database, China Biomedical Literature Service (SinoMed), Weipu Database (VIP), China National Knowledge Infrastructure (CNKI), http://ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) were searched from inception to March 2026. This review followed the PRISMA statement and assessed evidence with GRADE. The aim was to identify randomized controlled trials (RCTs) investigating the effects of ACER on cardiac function in patients with HF. Two investigators independently screened studies, extracted relevant data, and assessed the methodological quality using the Risk of Bias version 2 tool (RoB 2). Meta-analyses were performed using RevMan 5.3. The protocol was registered in PROSPERO (CRD420251184719). Eight RCTs involving 668 patients were included, seven conducted in China and one in Serbia. Compared with ER alone, ACER was associated with statistically significant improvements in left ventricular ejection fraction [LVEFl; MD = 4.98, 95% CI (2.77, 7.18)], 6-min walk distance [6MWD; MD = 77.78 m, 95% CI (59.23, 96.32)], left ventricular end-systolic diameter (LVESD) [MD = -5.27 mm, 95% CI (-7.83, -2.71)], Minnesota Living with Heart Failure Questionnaire (MLHFQ) score [MD = -6.41, 95% CI (-7.71, -5.10)], and left ventricular end-diastolic diameter (LVEDD) [MD = -5.65 mm, 95% CI (-6.81, -4.50)]. However, the certainty of the evidence was low or very low across all outcomes because of high risk of bias, substantial unexplained heterogeneity, imprecision, and uncertain publication bias. These findings should therefore be interpreted with extreme caution. The current evidence is insufficient to determine whether ACER provides clinically meaningful benefits over ER alone in patients with HF. Further high-quality RCTs are needed before ACER can be recommended as an evidence-based adjunct in HF rehabilitation. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251184719, identifier: CRD420251184719.

PMID 42465083
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