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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

PubMedInternational immunopharmacology2026-11-10

Targeted co-delivery of SPAG5 siRNA and a PD-L1 inhibitor using nanoliposomes enhances antitumor immunity in a murine prostate cancer model.

Huang Ruohui R, Jiang Bo B, Xu Gang G, Zhong Haidong H et al.

To investigate the role of SPAG5 in immune evasion of prostate cancer and to evaluate the anti-tumor and immunomodulatory effects of a PSMA-targeted liposome co-loading si-SPAG5 and BMS-202 (PSMA-Lipo@BMS/si-SPAG5). PSMA-Lipo@BMS/si-SPAG5 was prepared by the thin-film hydration followed by post-insertion method and its physicochemical properties were characterized. In vitro, the effects of the nanoparticles on PC-3 cell uptake, SPAG5 silencing efficiency, inhibition of the PI3K/AKT/PD-L1 pathway, immunogenic cell death (ICD), apoptosis, and immune cell functions were evaluated. An RM1-hPSMA syngeneic subcutaneous tumor model was established in immunocompetent C57BL/6 mice to assess the anti-tumor efficacy, immune microenvironment modulation, and safety of the nanoparticles. PSMA-Lipo@BMS/si-SPAG5 exhibited a size of 126.65 ± 7.9 nm and acid-responsive release characteristics. PSMA modification enhanced cellular accumulation in vitro and significantly improved tumor targeting in vivo. SPAG5 silencing inhibited the PI3K/AKT/PD-L1 axis, and together with BMS-202 contributing to PD-L1 inhibition, synergistically induced ICD-associated marker release and apoptosis. In immune cell co-cultures, the nanoparticles promoted CD8+ T-cell activation, NK cell cytotoxicity, and induced macrophage polarization toward the M1 phenotype. In vivo, the PSMA-Lipo@BMS/si-SPAG5 group showed the most significant tumor growth inhibition. After treatment, tumor tissues exhibited decreased Th2 cells, increased NK and Th17 cells, elevated CD8+ T-cell infiltration, reduced Tregs, a pro-inflammatory shift in cytokine profile, and no obvious toxicity. PSMA-Lipo@BMS/si-SPAG5 modulated the tumor immune microenvironment by silencing SPAG5 and inhibiting PD-L1, increasing antitumor immune cell infiltration and pro-inflammatory cytokines, and inhibiting prostate cancer growth.

PMID 43008433
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PubMedEnvironmental geochemistry and health2026-11-10

Multi-heterojunction CuO-WO3-ZnO/g-C3N4 nanohybrid for ultrasensitive electrochemical monitoring of losartan and visible light-assisted dye degradation.

Zhang Zhenshan Z, Feng Xia X, Long Yu Y, Wu Zhu Z et al.

This work reports the development of a multi-heterojunction CuO-WO3-ZnO/g-C3N4 nanohybrid as a multifunctional platform for visible-light-activated photocatalytic degradation of crystal violet dye and electrochemical sensing of the losartan. The CuO-WO3-ZnO/g-C3N4 nanohybrid was synthesized successfully and characterized systematically for its structural, optical, photocatalytic, and electrochemical properties. The CuO-WO3-ZnO/g-C3N4 nanohybrid demonstrated enhanced photocatalytic activity under visible light illumination towards the degradation of crystal violet dye, which was mainly due to enhanced visible light absorption, good interfacial charge separation, and fast charge transport between the heterojunction interfaces. The CuO-WO3-ZnO/g-C3N4-modified glassy carbon electrode exhibited excellent electrocatalytic activity towards losartan drug, which displayed an extremely low detection limit, a large linear response range, excellent reproducibility, repeatability, and stability, and high selectivity. In particular, the nanohybrid achieved approximately 97% degradation of crystal violet within 35 min, with a pseudo-first-order rate constant of 7.24 × 10⁻2 min⁻1. In addition, the developed electrochemical sensor exhibited a limit of detection (LOD) of 5.7591 × 10-8 M for losartan. The strong synergistic effect of CuO, WO3, ZnO, and g-C3N4 is confirmed by the increased charge migration rate and the availability of a high number of electrochemically and photocatalytically active sites, which leads to the enhanced performance of the multi-heterojunction nanohybrid for environmental monitoring and remediation of organic pollutants.

PMID 43007463
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PubMedCureus2026-11-10

Sequential Anti-HER2 (Human Epidermal Growth Factor Receptor 2) Therapy and Late-Line Tucatinib in Patients With HER2-Positive Breast Cancer and Brain Metastases: A Real-World Case Report.

Thakur Purnima P, Gupta Manish M, Kant Lalit C LC, Mehta Priya P et al.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with a high incidence of brain metastases (BMs), particularly among young and heavily pretreated patients, with intracranial disease remaining a major determinant of survival and quality of life (QoL). Tucatinib, a HER2-selective tyrosine kinase inhibitor (TKI), combined with trastuzumab and capecitabine, has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit, including in patients with active BMs. We present the case reports of two patients, both younger than 50 years, with HER2-positive metastatic breast cancer and biologically aggressive disease who progressed on prior anti-HER2 therapy (trastuzumab, lapatinib, and ado-trastuzumab emtansine (Ujvira™) in Case 1 and trastuzumab in Case 2) with worsening central nervous system involvement. Both were subsequently treated with tucatinib-based combination therapy (Tukavo™) later in the treatment sequence, once it became available and affordable, and showed clinical and radiological improvement. Case 1 had improvement in right-sided limb weakness and speech with no further seizures and remained clinically stable for seven months, and Case 2 had complete resolution of headache and vomiting, with Eastern Cooperative Oncology Group (ECOG) performance status improving from 2 to 1. QoL was assessed clinically from symptoms and performance status rather than with a validated instrument. This real-world experience illustrates the potential benefit of tucatinib-based regimens in young patients with aggressive HER2-positive breast cancer and BMs, even when used later in the treatment sequence. These findings are consistent with pivotal trial data in a resource-limited, real-world setting.

PMID 43004999
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PubMedChemical science2026-11-10

Quantum-accurate enhanced sampling and mini-protein folding through replica exchange for multiscale neural network potentials.

Solazzo Riccardo R, Gordiy Igor I, Riniker Sereina S

Neural network potentials (NNPs) have emerged as efficient alternatives to computationally demanding quantum-mechanical (QM) methods. AMPv3-EE-BMS25 (short AMP-BMS) is an equivariant NNP designed for multiscale ML/MM simulations that captures directional and long-range interactions. In classical molecular dynamics (MD) simulations, enhanced-sampling techniques are applied to cross large energy barriers and improve convergence. Among those, replica exchange with solute tempering (REST2) is an efficient method that selectively scales solute interactions while keeping the bath temperature fixed, thereby reducing the number of replicas required. Here, we present a REST2-like algorithm compatible with multiscale ML/MM simulations. This algorithm is combined with AMP-BMS by exploiting the separability of its Hamiltonian into solute-solute, solute-solvent, and solvent-solvent contributions. We validate the REST2-AMP approach on several peptidic systems in explicit solvent and demonstrate folding of the mini-proteins chignolin and CLN025 from extended conformations. Thus, our REST2 approach for ML/MM enables access to biologically relevant timescales while maintaining near-DFT accuracy.

PMID 43005958
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PubMedJournal of neuro-oncology2026-11-09

Pre-operative stereotactic radiosurgery versus intraoperative cesium-131 brachytherapy for resected brain metastases: a systematic review and meta-analysis.

Kite Trent T, Mahmoudi Danny A DA, Singh Eric E, Knox Henry H et al.

Pre-operative stereotactic radiosurgery (SRS) and intraoperative cesium-131 (Cs-131) brachytherapy are alternatives to post-operative SRS for resected brain metastases (BMs). The randomized phase 3 Radiation One and Done Study (ROADS; NCT04365374) showed improved surgical-bed control with Cs-131 tiles versus post-operative stereotactic radiotherapy, but outcomes relative to pre-operative SRS are undefined. PubMed, Embase, and ScienceDirect were searched through October 2026 (PRISMA 2020); one further trial was identified by other methods. Twelve-month local control (LC), leptomeningeal disease (LMD), radiation necrosis (RN), and overall survival (OS) were extracted for treatment-naïve BMs. Proportions were pooled with random-effects generalized linear mixed models and compared with a test for subgroup differences; sensitivity analyses included meta-regression, Hartung-Knapp, leave-one-out, follow-up, and fractionation analyses. Fifteen pre-operative SRS studies (918 patients/940 BMs) and four brachytherapy studies (207 patients/217 BMs) were included. Pooled 12-month LC was 97% (95% CI 90-99) with Cs-131 brachytherapy and 90% (86-93) with pre-operative SRS (test for subgroup differences p = 0.054; meta-regression p = 0.019; Hartung-Knapp p = 0.066); among studies reporting observed counts, LC was 99% vs. 90% (p = 0.009). Within pre-operative SRS, LC was 96% after hypofractionated and 86% after single-fraction treatment (p = 0.005). LMD (9.1% vs. 5.1%) and RN (0.7% vs. 5.2%) did not differ significantly. Median OS was 15.6 months with brachytherapy (range 5.9-42.5; 11.0 months, range 5.9-20.1, excluding the ROADS estimate) and 14.4 months with pre-operative SRS (range 6.3-26.4). Both approaches achieved high LC with low rates of LMD and RN. There was a trend towards higher LC with Cs-131 brachytherapy than with pre-operative SRS (97% vs. 90%; p = 0.054), and significantly so among studies reporting observed counts (99% vs. 90%; p = 0.009). Hypofractionated pre-operative SRS achieved LC similar to that of brachytherapy, suggesting that the difference may reflect single-fraction dose de-escalation rather than an intrinsic advantage of either modality. The two techniques may serve complementary roles, and prospective comparative study is warranted. This review was not registered in PROSPERO.

PMID 43002189
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PubMedmicroPublication biology2026-11-08

The C. elegans pharyngeal basement membrane has a high affinity for binding agrin.

Ibeanu C Teresa CT, Srinivasan Sandhya S, Chi Qiuyi Q, Sherwood David R DR

Basement membranes (BMs) are dense, sheet-like extracellular matrices that surround animal tissues and provide mechanical and signaling functions. Tissue BMs are compositionally unique, with the presence and abundance of numerous components tailored to meet tissue-specific needs. How BMs establish and maintain distinct compositions remains poorly understood. Here, we investigate how the BM protein agrin is uniquely concentrated in the C. elegans pharyngeal BM. Through tissue-specific expression and live imaging, our results suggest that a combination of pharyngeal-specific expression and high BM affinity for binding agrin ensures the unique enrichment of agrin in the pharyngeal BM.

PMID 42997129
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