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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

PubMedClinical genitourinary cancer2026-09-18

Assessment of Bone Metastases, Skeletal-Related Events and Bone-Targeting Agents in Patients With Metastatic Renal Cell Carcinoma Receiving First-Line Systemic Therapy (Meet-URO 33 Study Subanalysis).

Valsecchi Anna Amela AA, Rebuzzi Sara Elena SE, Cursano Maria Concetta MC, Pantano Francesco F et al.

Bone metastases (BMs) in patients with metastatic renal cell carcinoma (mRCC) negatively affect survival, quality of life, and increase the risk of skeletal-related events (SREs). Evidence remains limited in the era of first-line immune-based combinations. Meet-URO 33 is an Italian multicenter observational retrospective-prospective study enrolling mRCC patients receiving first-line therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), clinical characterization, incidence of SREs, and impact of bone-targeting agents (BTAs). Survival was analyzed using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. A total of 1696 patients enrolled between 2021 and 2025 were included; 526 (31%) had BMs at metastatic diagnosis. Patients with BMs more frequently had poorer performance status and unfavorable International mRCC Database Consortium (IMDC) risk. The presence of BMs was associated with significantly worse OS (median 26.9 vs. 102.1 months; hazard ratio [HR] 0.53; P < .001) and worse PFS (median 14.2 vs. 19.4 months; HR 0.71; P < .001), with OS and PFS varying according to first-line regimen. Worse OS persisted across IMDC risk classes and treatment types; PFS differences were not significant in favorable/intermediate IMDC risk groups and with tyrosine kinase inhibitor monotherapy. Neither anatomical site nor number of BMs significantly affected OS. SRE incidence in patients with BMs was 26.8%, more frequent with spinal, rib, or other-site involvement, and more common in BTA-treated patients (22.2% vs. 13.7%, P = .03), likely reflecting selection bias. BMs are confirmed a negative prognostic factor in mRCC involving persistent unmet clinical needs.

PMID 42760246
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PubMedApplied biochemistry and biotechnology2026-09-18

Shaoyao Decoction Inhibits Colorectal Cancer Progression by Targeting PD-L1 to Reprogram the Immunosuppressive Tumor Microenvironment.

Wang Xiaoyan X, Mima Zhuoga Z, Sai Wujie W, Song Lijuan L et al.

Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype accounting for ~ 85% of cases, remains refractory to immune checkpoint inhibitors due to persistent immunosuppression. Shaoyao Decoction (SYD), a traditional Chinese herbal formula, is known for its anti-inflammatory and anticancer effects. However, the mechanisms by which it modulates immune responses in colorectal cancer (CRC) remain poorly understood. Here, we evaluated SYD's efficacy in AOM/DSS-induced colitis-associated CRC and PD-L1-overexpressing MC38 syngeneic models, using the PD-1/PD-L1 inhibitor BMS-202 as a positive control. In vivo, SYD significantly suppressed tumor growth, normalized colon structure, and reduced tumor burden, with efficacy comparable to BMS-202 but without overt toxicity. Mechanistically, SYD downregulated PD-L1 expression in tumor and spleen tissues, shifted serum cytokines toward a pro-inflammatory profile characterized by increased IL-2 and IFN-γ as well as decreased IL-10 and TGF-β, and restored CD4⁺/CD8⁺ T cell balance. In vitro, SYD inhibited the viability of PD-L1-overexpressing MC38 cells and reduced PD-L1 mRNA expression. Collectively, SYD exerts potent anti-CRC effects by targeting PD-L1 to remodel the immunosuppressive tumor microenvironment. As a multi-target agent, it holds great promise for MSS-CRC, bridging TCM with modern immuno-oncology.

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PubMedMolecular neurobiology2026-09-17

Impact of Losartan Nanoparticles on Carbon Tetrachloride-induced Cerebellar Injury in Rats: Association with Alterations in RIPK1/RIPK3/MLKL Necroptosis Markers.

Lashine Nermeen H NH, Elhessy Heba M HM, Hammad Maha O MO, Farrag Eman A E EAE et al.

Carbon tetrachloride (CCL₄) is a lipophilic industrial solvent metabolized by cytochrome P450 enzymes. Its rapid diffusion across membranes facilitates widespread tissue distribution, including the brain, where it induces oxidative stress and alters the expression of necroptosis-related markers, including tumor necrosis factor-alpha (TNF-α). Losartan, an angiotensin II receptor antagonist, has demonstrated attenuation of cerebellar injury in many neurodegenerative diseases. This study evaluated the potentials of losartan and its nanoparticle formulation against CCL₄-induced cerebellar injury. Twenty-four adult male Sprague-Dawley rats were assigned into four groups: Control, CCL₄, Losartan, and Losartan potassium nanoparticles (LP-NPs)-treated groups. Oxidative stress parameters, quantitative Real time- PCR (qRT-PCR) for Tnf-α, receptor interacting protein kinase 1 (Ripk1), receptor interacting protein kinase 3 (Ripk3), and mixed lineage kinase domain-like protein (Mlkl), along with histological and immunohistochemical (IHC) assessments, were performed. CCL₄ exposure significantly elevated malondialdehyde (MDA) while reducing superoxide dismutase (SOD), reduced glutathione (GSH), and catalase. Molecular study shows upregulation of mRNA expression of Tnf-α, Ripk1, Ripk3, and Mlkl, which correlates with alterations in necroptosis-related marker expression. IHC showed marked increases in RIPK1, RIPK3, Glial Fibrillary Acidic Protein (GFAP), and Ionized calcium-binding adaptor molecule1 (Iba1) immunoreactivity, with a concomitant decrease in caspase-8. Histologically, CCL₄ induced severe cerebellar alterations, including reduced myelinated fiber area, Purkinje cell loss, and granular layer thinning. Both Losartan- and LP-NPs-treated groups significantly mitigated these biochemical, molecular, and histological changes, with LP-NPs exerting greater observed effects in histological parameters and selected IHC markers. Both treatments produced comparable reductions in qRT-PCR mRNA expressions of Tnf- α , Ripk1, and Ripk3. In conclusion, losartan, particularly in nanoparticle form, attenuates CCL₄-induced cerebellar toxicity and is associated with alteration in necroptosis-related markers and attenuation of GFAP and Iba1 immunoreactivity, accompanied by structural improvement. These findings highlighted LP-NPs as a prospective biochemical, molecular, and histological protective agent against CCL₄-induced cerebellar injury. Further studies are required to confirm the direct involvement of the RIPK1/RIPK3/MLKL necroptosis pathway.

PMID 42749941
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PubMedAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026-09-17

Targeting the CRYAB/β-Catenin Axis with an MMP-9-Responsive Hydrogel Disrupts CTC Clusters to Suppress Progression of Hepatocellular Carcinoma after Radiofrequency Ablation.

Chen Hui H, Yang Danni D, Pi Songying S, Liu Yuhan Y et al.

Incomplete radiofrequency ablation (iRFA) represents a major clinical challenge in hepatocellular carcinoma (HCC) management, as residual tumors acquire enhanced metastatic potential through undefined mechanisms. Herein, we report that sublethal thermal stress upregulates the heat-responsive molecular chaperone CRYAB, which stabilizes β-catenin protein by inhibiting its ubiquitin-mediated proteasomal degradation. The CRYAB/β-catenin axis drives epithelial-mesenchymal transition (EMT) in residual HCC cells and simultaneously polarizes tumor-associated neutrophils (TANs) toward the pro-tumorigenic N2 phenotype. This dual regulation pre-programs a pro-metastatic microenvironment in situ, promotes the formation of heterotypic circulating tumor cell (CTC) clusters, and ultimately accelerates tumor recurrence and metastasis post-iRFA. To suppress this pathological cascade, we engineered a matrix metalloproteinase-9 (MMP-9)-responsive thermosensitive hydrogel system (XB@Gel) that enables localized and sustained co-delivery of the β-catenin inhibitor XAV-939 and the PD-L1 inhibitor BMS-202. XB@Gel effectively reverses EMT, reprograms the immunosuppressive microenvironment, reduces CTC clusters, and robustly inhibits HCC recurrence and metastasis after iRFA. Collectively, our findings identify the CRYAB/β-catenin axis as a key transducer of thermal stress into a pro-metastatic signaling cascade in residual HCC and establish XB@Gel as a promising multi-dimensional therapeutic strategy to combat post-iRFA progression.

PMID 42750293
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PubMedData in brief2026-09-17

An annotated dataset of Building Management System periodic alarms.

Verdière Mathias M, Marié Sylvain S, Knecht Pablo P

This article presents alarm events data collected from 22 Building Management Systems (BMS) from 9 countries (mainly European) and 7 market segments (Commercial, Education, Entertainment, Government, Healthcare, Residential, Transport) over a period of 1 month. 321 alarm event timeseries were collected. Each series corresponds to a single (unknown) user-defined alarm rule switching from "inactive" (reset) to "active" (alarm) state and back. Such a rule usually consists in a simple upper or lower threshold applied to an observed variable such as a room temperature sensor, a valve pressure, etc. - possibly with hysteresis, delays, or Boolean logic combining several thresholds. Only change of state events are recorded in the dataset, together with the new state after transition. Timestamps are provided raw without any uniformization resampling, preserving the original time resolution of the series. With a volume of 110,457 alarm events ranging from 11 to 13,032 events per series, this dataset illustrates the diversity of alarm events patterns in buildings, and challenges associated with non-uniform sampling. Researchers may wish to leverage it to benchmark the execution time and performance of pattern mining, machine learning and AI approaches. Example tasks include modelling and mining of single series (periodicity detection, temporal clustering, frequent pattern mining…) or multiple series (clustering, frequent pattern mining…). Approaches may leverage the complete binary (alarm/reset) state timeseries or prefer to filter the reset events to focus solely on activation events sequences. To encourage comparable reproducible results for learning tasks, the dataset is split into predefined train and test files containing 237 and 84 series respectively. The training data corresponds to May 2024 while the test data is from Jan-Feb 2026. The test data originates from one building that is strictly distinct from training data. For this reason, researchers may wish to use the test dataset for validation purposes and interpret associated results as hints of generalization capabilities of the candidate approach under test. The names of the series are fully anonymized, with names spanning from A0 to A236 and from A1000 to A1083. Finally, each timeseries was presented to a panel of subject matter experts to annotate it as periodic or non-periodic according to a consensus of votes. Two kinds of periodicity labels were considered: "is repeat periodic", representing a perception that the time duration between consecutive alarm events is regular, and "is daily periodic", representing a perception that there are typical daily patterns that occur frequently in the series. These two labels may be used to evaluate periodicity detection algorithms, whether supervised (classification task) or unsupervised (clustering task). Both labels may be combined with a logical OR to create a broader "is periodic" label.

PMID 42751455
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PubMedNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026-09-16

Acute effects of AT1 receptor blockade on approach-avoidance of negative emotional faces.

Prasad Divya D, Pelster Ina I, Outes Leonardo L, Gillespie Amy A et al.

Recent evidence implicates the renin angiotensin system (RAS) in various cognitive markers of depression, including dysfunctional reward processing. Yet, it remains unknown whether these effects extend to other markers implicated in depression and its treatment, such as approach-avoidance motivations that reflect innate drives to approach reward and evade harm. We sought to examine the impact of acute losartan, an angiotensin type 1 (AT1) receptor blocker, on the implicit approach-avoidance of facial expressions and checkerboard controls in healthy adults. In a randomized controlled trial, N = 68 healthy adults aged 18-50 (49 F/19 M) were administered a single 50 mg dose of losartan or placebo before completing an implicit Approach Avoidance Task (AAT) at drug-peak level. On the AAT, participants responded to color-filtered facial stimuli (happy, sad, angry, or neutral) and checkerboard controls using a joystick, and were instructed to pull all gray photos and push all brown photos as quickly as possible. Compared to placebo, losartan induced a significant avoidance bias for sad faces (p = 0.027) and reduced avoidance of angry faces at trend level (p = 0.085). This occurred without significant group differences on blood pressure, overall reaction time, accuracy, and approach-avoidance biases for other stimuli. The response pattern associated with AT1 receptor blockade may counteract previously observed depressive tendencies, suggesting effects possibly consistent with antidepressant treatments. Our findings further highlight the RAS as a mechanistically relevant target for psychiatry, suggesting that AT1 receptor antagonism may have relevance for treating depression and other emotional disorders characterized by aberrant motivational biases (Clincialtrials.gov ID: NCT06624904).

PMID 42745010
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