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losartan + HCTZ (Gizaar / Hyzaar / Cozaar plus)

✓ Approved

Merck & Co. · AGTR1 · 小分子

什么是 losartan + HCTZ？

losartan + HCTZ 是一种小分子，由Merck & Co.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Gizaar, Hyzaar, Cozaar plus
公司Merck & Co.
药物类别小分子
分子靶点AGTR1, SLC12A3
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Merck & Co.

作用机制

分子靶点

losartan + HCTZ 作用于 2 个分子靶点：

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
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

losartan + HCTZ 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersHypertension✓ Approved

相关研究文献

PubMedJournal of medicinal chemistry2026-09-10

Structure-Function Analysis of the Benzyloxy Moiety of the Delta-Opioid Receptor Positive Modulator BMS-986187: Identification of a Derivative with High Selectivity for the Delta-Opioid Receptor over the Mu-Opioid Receptor In Vitro and In Vivo.

Li Mengchu M, Zhang Sherrice S, Powell Alexander J AJ, Stewart Hannah C HC et al.

Positive allosteric modulators (PAMs) of the delta-opioid receptor (DOR) enhance endogenous opioid signaling while avoiding the convulsant liability of orthosteric agonists. However, the prototypical DOR-PAM, BMS-986187, also potentiates mu-opioid receptor (MOR) signaling, raising concerns regarding respiratory depression and abuse liability. Here, we report a structure-activity study of the benzyloxy moiety of BMS-986187 to improve selectivity for DOR over MOR, while retaining DOR-PAM potency. Fifty-two new analogues and 12 previously reported ones featuring mono- and disubstitution of the benzyl ring and phenyl-heterocycle replacements were synthesized and evaluated in β-arrestin2 recruitment assays. Ortho-substituted derivatives consistently enhanced DOR-PAM potency, although often increased MOR-PAM activity. One pyridyl derivative (compound 35) retained high DOR-PAM potency and efficacy (EC50 = 0.1 μM, Emax = 91%) with no detectable MOR activity. In mice, compound 35 enhanced DOR-mediated reversal of nitroglycerin-induced hyperalgesia, an effect absent in DOR-knockout mice, without enhancing MOR-mediated antinociception, demonstrating in vivo selectivity.

PMID 42720491
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PubMedJournal of neuro-oncology2026-09-09

Stereotactic radiosurgery for brain metastases from male breast cancer: a multicenter retrospective study.

Duzkalir Ali H AH, Askeroglu Mehmet O MO, Yildirim Dogu C DC, Marciniuk Kristen K et al.

Brain metastases (BMs) from male breast cancer (MBC) are exceptionally rare, and the efficacy and safety of stereotactic radiosurgery (SRS) in this population remain poorly characterized. We conducted a multicenter retrospective cohort study across 12 institutions. Eligible patients had histologically confirmed MBC with histopathologically or radiologically documented BMs treated with SRS. Lesion-level outcomes were analyzed using generalized estimating equations (GEE) with robust variance estimation. Overall survival (OS) was estimated by the Kaplan-Meier method. Neurological symptom change was assessed with McNemar's exact test, and discriminative ability of dosimetric variables for local failure was evaluated using receiver operating characteristic (ROC) analysis. Nineteen patients harboring 185 SRS-treated lesions were included. Median age at SRS was 59.0 years. The overall crude local control rate was 97.3%. Median OS was 28.0 months. Patients with controlled systemic disease at SRS demonstrated significantly longer median OS than those without (40.0 vs. 22.0 months; p = 0.032). Target volume was the only significant discriminator of local failure on ROC analysis (p < 0.001; optimal threshold 0.98 cc) and independently predicted adverse radiation effects on GEE analysis (p = 0.013). Neurological symptom burden decreased significantly after SRS (63.2% to 26.3%; p = 0.016), and median Karnofsky Performance Status remained stable. SRS achieves high local control with a favorable safety and neurological profile in MBC BMs. Systemic disease control at the time of SRS is the primary determinant of survival, while target volume is the principal dosimetric predictor of both local failure and radiation toxicity. These findings support the application of established SRS practice parameters in this rare population.

PMID 42714633
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PubMedBehavioural brain research2026-09-09

Astragalus membranaceus-derived exosomes alleviate traumatic brain injury by inhibiting SERPINE1/HIF-1α/NLRP3-mediated pyroptosis.

Lyu Jinlong J, Sun Peng P, Liao Zhengluan Z, Li Chao C

Pyroptosis is recognized as a critical contributor to the secondary injury following traumatic brain injury (TBI), and its inhibition has been shown to preserve neuronal integrity and improve neurological outcomes. This study aimed to investigate the therapeutic effects of Astragalus membranaceus (AM)-derived exosomes on TBI-induced pyroptosis and elucidate the underlying mechanism. AM-derived exosomes were purified via sucrose density gradient ultracentrifugation and subsequently characterized. The effects of AM-derived exosomes in TBI were assessed in HT22 neuronal cells subjected to scratch injury and in a controlled cortical impact (CCI) mouse model of TBI. Neurological outcomes were evaluated through histopathological staining, neurologic severity scoring, grip strength testing and neurological function evaluation. Pyroptosis was detected using flow cytometry following caspase-1 and propidium iodide staining. NLRP3 activator BMS-986299 was used to determine whether activation of NLRP3 could reverse the inhibitory effects of AM-derived exosomes on pyroptosis. AM-derived exosomes significantly enhanced cell viability and reduced neuronal pyroptosis and pyroptotic markers (cleaved caspase-1, GSDMD-N, IL-1β and IL-18), alongside downregulating SERPINE1, HIF-1α, and NLRP3 expression. Activation of NLRP3 by BMS-986299 partially abolished the anti-pyroptotic effects mediated by AM-derived exosomes. In vivo, systemic administration of AM-derived exosomes ameliorated neurological deficits, improved motor function, attenuated hippocampal neuronal loss, and suppressed SERPINE1/HIF-1α/NLRP3 signaling. AM-derived exosomes showed excellent biocompatibility and the ability to penetrate the blood-brain barrier. These findings demonstrate that AM-derived exosomes represent a promising therapeutic approach for TBI by suppressing pyroptosis and facilitating functional recovery through inhibition of the SERPINE1/HIF-1α/NLRP3 axis.

PMID 42716132
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PubMedClinical medicine insights. Case reports2026-09-08

Dual Thiol Drug-Induced Insulin Autoimmune Syndrome in a Non-Asian Patient Carrying HLA-DRB1*04:06: A Case Report and Literature Review.

Adi Mohammad M, Umarov Doniyor D, Oqboyev Zairullo Z, Smerat Aseel A et al.

Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare cause of endogenous hyperinsulinemic hypoglycemia classically linked to high-titer insulin autoantibodies and exposure to sulfhydryl (-SH)-containing drugs. IAS is strongly HLA-associated and is most frequently reported in East Asian populations. We report a case in which simultaneous exposure to two thiol-containing agents unmasked IAS in a non-Asian patient carrying HLA-DRB1*04:06. A 60-year-old woman developed recurrent autonomic and neuroglycopenic episodes 2-4 hours after meals. Home medications included captopril and over-the-counter α-lipoic acid (ALA). During a symptomatic episode her plasma glucose was 38 mg/dL with markedly elevated serum insulin, C-peptide and proinsulin; mixed-meal testing reproduced a postprandial glucose peak followed by profound hypoglycemia accompanied by paradoxical hyperinsulinemia. Insulin autoantibodies were strongly positive (>150 U/mL) and HLA genotyping revealed DRB1*04:06. A supervised fast was non-diagnostic for insulinoma. Management comprised immediate discontinuation of both captopril and ALA (captopril replaced with losartan) and dietary measures (frequent small low-carbohydrate meals). Hypoglycemic episodes abated within two weeks and resolved by six weeks; fasting glucose, insulin and IAA titers had substantially improved by three months. To our knowledge, this is the first reported case of IAS temporally associated with concurrent captopril and ALA exposure in a non-Asian carrier of HLA-DRB1*04:06. The case highlights the need to review both prescription drugs and supplements when investigating hyperinsulinemic hypoglycemia, that IAS can occur outside typical ethnic groups when permissive HLA alleles are present, and that prompt withdrawal of offending agents with conservative measures often leads to spontaneous remission.

PMID 42707574
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PubMedThe Journal of biological chemistry2026-09-07

Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells.

Weckerly Claire C CC, Murtagh Olivia L OL, Swayhoover Tiernan T, Pemberton Joshua G JG et al.

Phosphatidic acid (PA) is an essential intermediate generated during phospholipase C (PLC) signaling, but its regulation is complex. PA can be generated by ten different diacylglycerol kinase paralogs (DGKs) and two different phospholipase D paralogs (PLDs) in mammals. Because these enzymes are activated under diverse conditions and at various membranes, understanding paralog-specific contributions to PA production is critical for therapeutic development of drugs that modulate the PLC pathway. To address this, we aimed to characterize the paralog specificity of the DGK inhibitors R59022 and BMS-502 against individual endogenously-tagged DGK paralogs in live cells. We found that R59022 and BMS-502 both recruited endogenous DGKα to the plasma membrane, and inhibited the catalytic fragment of DGKα when ectopically localized to the mitochondrial outer membrane. However, at its effective dose, R59022 paradoxically increased PA levels, while BMS-502 functioned as a potent inhibitor. Live-cell imaging experiments using BMS-502 with carbachol stimulation of endogenous muscarinic receptors showed that inhibition of both DGKα and the PLDs is needed to substantially reduce PA levels during PLC activation. Our findings both identify paralog-specific druggable targets for modulating PLC signaling events, and establish a new platform for characterizing DGK and PLD activity in living cells.

PMID 42705541
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PubMedFoot & ankle specialist2026-09-07

Cartilaginous Non-Structural Allografts in the Management of Foot and Ankle Pathologies.

Rubin Jared J, Tham Alexander A, Allen Michael M, Butler James J JJ et al.

BackgroundCartilaginous non-structural allografts have emerged as biologic adjuncts for the treatment of osteochondral lesions and focal cartilage pathology in the foot and ankle, particularly for lesions that fail bone marrow stimulation (BMS) yet may not warrant osteochondral transplantation. These allografts may serve as an intermediary treatment strategy between BMS and more invasive restorative procedures.MethodsA scoping review of the currently available literature regarding cartilaginous non-structural allografts used in foot and ankle pathology was performed, with a focus on BioCartilage, DeNovo NT, and CartiMax.ResultsBioCartilage may improve radiographic defect fill when used as an adjunct to marrow stimulation procedures, although superior functional outcomes have not been consistently demonstrated. In contrast, DeNovo NT has demonstrated mixed clinical and radiographic outcomes, including persistent postoperative marrow edema, inconsistent graft incorporation, and relatively high complication and failure rates in current studies. Available evidence for BioCartilage and DeNovo NT consists primarily of small clinical studies with heterogeneous methodologies, whereas evidence for CartiMax remains limited to preclinical and industry-supported investigations without published peer-reviewed human clinical outcome studies.ConclusionAlthough these allografts demonstrate potential as biologic adjuncts for cartilage repair, currently available evidence remains limited by heterogeneous study designs, inconsistent outcome reporting, limited comparative data, small cohort sizes, and short-term follow-up. Cost-effectiveness remains an important consideration, given the limited evidence demonstrating long-term functional superiority over traditional marrow stimulation techniques. Further high-quality comparative studies are necessary to determine the long-term efficacy, safety, durability, and cost-effectiveness of cartilaginous non-structural allografts in foot and ankle pathology.Level of Evidence:V: Scoping Review.

PMID 42704057
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