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losartan + HCTZ (Gizaar / Hyzaar / Cozaar plus)

✓ Approved

Merck & Co. · AGTR1 · Small Molecule

What is losartan + HCTZ?

losartan + HCTZ is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesGizaar, Hyzaar, Cozaar plus
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetAGTR1, SLC12A3
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

losartan + HCTZ acts on 2 molecular targets:

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

losartan + HCTZ is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedBritish journal of clinical pharmacology2026-08-29

Clinical relevance of pharmacogenomic information for improving prescribing practices in acutely admitted older medical patients.

Christensen Louise Westberg Strejby LWS, Boas Anne Kirstine AK, Clausen Emilie E, Koch Nicoline Elers NE et al.

Safe prescribing and effective medication review during acute hospitalization depends on accurate information about liver and kidney function because these organs are responsible for the elimination of most medications. While estimates for kidney function are widely used, comparable markers of hepatic drug-metabolizing capacity are not routinely available. We evaluated the clinical relevance of pharmacogenomic (PGx) information for key pharmacogenes implicated in medication elimination in older adults presenting to the emergency department. Fourteen pharmacogenes were analysed using the Personal Medicine Profile™ test. GeneYouIn PillCheck™ software performed genotype-to-phenotype translations, identified drug-gene interactions (DGIs) and generated a clinical decision report based on each patient's actual medication use. Among 125 acutely admitted older medical patients (median age 78.3 years; 10 medications; 7 chronic diseases), PGx testing identified 88 DGIs across 63 patients (50.4%). Of these, 46.5% were considered by clinical experts to be clinically relevant for the individual patient, affecting 33 patients (26.4%) in the total study population. Frequently implicated pharmacogenes included CYP2C19 (25.0%), SLCO1B1 (25.0%), CYP2D6 (20.5%), CYP2C9 (14.8%) and OPRM1 (6.8%), and frequently implicated medications included losartan (13.6%), pantoprazole (12.5%), simvastatin (12.5%), atorvastatin (11.4%) and metoprolol (11.4%). With more than one-quarter of acutely admitted older medical patients having one or more clinically relevant DGIs, these findings suggest that PGx information may have meaningful clinical utility for improving prescribing practices in acute care. However, interpretation in this population requires careful consideration of other factors such as nutritional status and inflammation that may modify pharmacogene activity.

PMID 42666103
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PubMedNeuroscience letters2026-08-28

Asc-1/SLC7A10 regulates NMDA receptor co-agonist availability at hypoglossal motoneurons.

Roob Patrick P, Hülsmann Swen S

The Asc-1/SLC7A10 transporter regulates extracellular levels of the NMDA receptor co-agonists glycine and D-serine, yet its role at excitatory synapses in the brainstem remains poorly understood. We investigated how pharmacological Asc-1 blockade modulates NMDA receptor-mediated synaptic transmission at hypoglossal motoneurons and whether glycine or D-serine is the functionally dominant co-agonist at these synapses. Whole-cell patch-clamp recordings were performed in Mg2+-free ACSF from hypoglossal motoneurons in brainstem slices of neonatal mice. Bath application of the selective Asc-1 inhibitor BMS-466442 (10 µM) significantly increased NMDA receptor-mediated mEPSC amplitude and tonic holding current, without affecting mEPSC frequency. Exogenous glycine (1 mM) robustly potentiated mEPSC amplitude and frequency both in the absence and presence of BMS-466442, whereas D-serine selectively increased tonic holding current in an Asc-1-dependent manner. Three-way ANOVA confirmed a significant co-agonist type × condition interaction, with glycine more effective than D-serine at potentiating phasic synaptic responses. These findings identify Asc-1 as a regulator of NMDA receptor co-agonist availability at brainstem excitatory synapses and suggest that glycine, rather than D-serine, is the dominant synaptic co-agonist at mouse hypoglossal motoneurons.

PMID 42665207
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PubMedBiomedicines2026-08-27

Temporal Dynamics of PD-L1 Surface in RKO Cells: Characterizing the Reversible Impact of the Small-Molecule Dimerizer BMS-202.

Sevoyan Gohar G, Polianczyk Daniel D, Grabska Siranuysh S, Grabski Hovakim H et al.

Background/Objectives. Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint protein that enables tumors to evade immune surveillance by suppressing T cell activation. Monoclonal antibodies are currently used to modulate PD-1/PD-L1 interactions. However, several immune-associated adverse effects were ascribed to those treatments. This led to the necessity for small-molecule alternatives like BMS-202. Methods. In this study, we investigated the temporal dynamics of cell-surface PD-L1 in response to the small-molecule dimerizer BMS-202. Treatment with a non-cytotoxic concentration of BMS-202 at 5 µM triggered a transient reduction in surface PD-L1 concentration, reaching its lowest level at 15 min. In the attempt to characterize the fate of PD-L1 following exposure to the BMS-202 dimerizer, we employed a low-pH wash internalization assay. Results. The results demonstrated a transient increase in intracellular PD-L1 within 5-15 min of compound exposure, followed by rapid recovery of surface PD-L1 levels. These findings suggest that BMS-202-induced changes in surface PD-L1 are acute and reversible, with levels returning to baseline within 24 h post-exposure. Conclusions. These findings reveal a dynamic regulatory mechanism where small-molecule-induced dimerization triggers rapid protein trafficking and transient surface depletion. Understanding these temporal dynamics is essential for the development of next-generation small-molecule immune checkpoint inhibitors.

PMID 42652042
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PubMedBiomedicines2026-08-27

Systemic Use of Oral Rapamycin, Prednisone and Colchicine After Coronary Bare-Metal Stent Implantation: Narrative Review of Randomized Clinical Trials.

Fernandez-Pereira Carlos C, Rodriguez Alfredo E AE

Background: Coronary stenting remains the cornerstone of interventional cardiology. Drug-eluting stents (DES) have reduced restenosis compared to bare-metal stents (BMS), but their high cost and need for prolonged dual antiplatelet therapy (DAPT) limit accessibility in many regions. Recent evidence has revisited the potential role of systemic pharmacologic adjuncts-oral sirolimus (rapamycin), prednisone and colchicine-as cost-effective therapies to mitigate restenosis and adverse events following BMS implantation. Objective: This review critically evaluates the clinical and mechanistic evidence supporting the use of oral immunosuppressive or anti-inflammatory drugs following BMS implantation, with emphasis on their applicability in both resource-limited and general cardiology settings. Three randomized clinical trials comparing this strategy against DES are analyzed and discussed in this review. Conclusions: Oral sirolimus, prednisone, and colchicine demonstrate promising anti-inflammatory and antiproliferative effects that translate into clinical outcomes comparable to DES in a highly select population. Their systemic administration following BMS implantation may provide a feasible, cost-effective alternative where DES use is restricted by cost or clinical contraindications. Larger-scale, long-term trials are warranted to confirm safety, optimize dosing, and identify ideal patient populations for this "pharmacologic stent hybrid" strategy.

PMID 42652068
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PubMedMicroorganisms2026-08-27

Stage-Specific Dynamic of Gut Microbiota Across the Musk-Secretion Cycle in Forest Musk Deer (Moschus berezovskii).

Wei Gangning G, Ji Jianhao J, Feng Mengheng M, Xiao Zhixiang Z et al.

Musk secretion in forest musk deer (Moschus berezovskii) involves unique physiological processes, yet the paradox of heightened energy expenditure concurrent with voluntary fasting during this period remains poorly understood. Given the role of gut microbiota in host energy metabolism and health, we characterized its compositional and functional dynamics across the musk-secretion cycle. Fecal samples were collected from male forest musk deer at three stages-before (BMS), during (DMS), and after musk secretion (AMS)-and analyzed via full-length 16S rRNA gene sequencing. Results showed that alpha diversity differed significantly among groups (Simpson index: p = 0.027). Beta diversity analysis revealed significant community restructuring across stages (Adonis, R2 = 0.173, p < 0.01), while LEfSe analysis (LDA > 4.0) identified a series of stage-specific taxa, further corroborating the existence of inter-group differences. In terms of species composition, Firmicutes and Bacteroidetes dominated across all stages. Significant inter-stage differences were observed in Verrucomicrobiota (highest in DMS), Patescibacteria (lowest in DMS), Proteobacteria (progressively declining), and Actinobacteria (progressively declining). At the genus level, Akkermansia, Candidatus Saccharimonas, Roseburia, and Butyricicoccus showed significant variation across the musk-secretion cycle. Notably, Akkermansia muciniphila varied significantly across stages despite high inter-individual variability. Functional prediction revealed the enrichment of hydrocarbon degradation and nitrogen fixation in BMS, and anaerobic respiration and reductive acetogenesis in DMS. This study provides foundational insights into the gut microecological mechanisms underlying musk secretion in forest musk deer.

PMID 42655177
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PubMedFrontiers in neuroscience2026-08-27

Multimodal DeepSurv model with SHAP-based interpretation for predicting local failure in patients with brain metastases undergoing hypofractionated stereotactic radiotherapy.

Jin Long L, Zhao Qifan Q, Xiao Ying Y, Hu Yuan Y et al.

Local Progression-Free Survival (LPFS) is an important clinical endpoint following hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs). However, accurate prediction of local failure risk remains challenging because conventional clinical factors do not fully capture tumor heterogeneity. Therefore, we aimed to develop and validate an explainable radiomics-based deep learning survival model to predict LPFS after HSRT and identify patients at elevated risk of local failure. This retrospective study included 100 patients with BMs treated with HSRT between 2019 and 2023 as training dataset, while utilized medical images and clinical features from 40 patients from publicly available dataset PROTEAS project. Radiomic features were extracted from the contrast-enhancing BM (T1-weighted contrast-enhanced MRI) and edema (T2-FLAIR MRI). A baseline Cox proportional hazards model incorporating clinical variables was established for comparison. Three DeepSurv models were developed using different combinations of clinical, BM-derived, and edema-derived radiomic features. Model performance was evaluated using the concordance index (C-index). Kaplan-Meier analysis was performed for risk stratification, and Shapley Additive Explanations (SHAP) were used to identify the most influential prognostic features. The best predictive performance was achieved by the DeepSurv model integrating clinical, BM-derived, and edema-derived radiomic features, outperforming the clinical-only Cox model (C-index: 0.61 vs. 0.72). The model effectively stratified patients into distinct prognostic groups with significantly different local failure-free survival outcomes (P = 0.002). SHAP analysis identified edema Gray Level Co-occurrence Matrix (GLCM) Cluster Prominence as the most important predictor of local failure, followed by edema Large Area High Gray Level Emphasis (LAHGLE), tumor GLCM Cluster Prominence, and tumor LAHGLE. Patients with high edema GLCM Cluster Prominence exhibited significantly worse local failure-free survival than those with low values (P = 0.0155). A combination of clinical, tumor-derived, and edema-derived radiomic features predicted Local Progression-Free Survival more accurately than clinical variables alone. Peritumoral edema features contributed more strongly to local failure prediction than tumor features, highlighting the prognostic importance of the tumor microenvironment. Patients received targeted therapy with low-risk radiomic profiles benefit from HSRT for local control.

PMID 42656372
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