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umeclidinium bromide + vilanterol (642444+573719 / Anoro / GSK573719/GW642444)

✓ Approved

Innoviva, Inc. · ADRB2 · 小分子

什么是 umeclidinium bromide + vilanterol？

umeclidinium bromide + vilanterol 是一种小分子，由Innoviva, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Inhaled。

药物档案

商品名642444+573719, Anoro, GSK573719/GW642444
公司Innoviva, Inc.
药物类别小分子
分子靶点ADRB2, NR3C1
给药途径Inhaled
状态Approved
来源： ClinicalTrials.gov, Innoviva, Inc.

作用机制

分子靶点

umeclidinium bromide + vilanterol 作用于 2 个分子靶点：

ADRB2adrenoceptor beta 2 (B2AR, ARB2)
NR3C1nuclear receptor subfamily 3 group C member 1 (GR, GCCR)
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

umeclidinium bromide + vilanterol 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
Respiratory, thoracic and mediastinal disordersChronic obstructive pulmonary disease✓ Approved

相关研究文献

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Selective Fractionation of Larch into Oligosaccharides and Less-Condensed Lignin in a Novel Molten Salt/n-Butanol System.

Huang Yuetong Y, Zhang Xinyan X, Liu Qiyu Q, Ma Qiaozhi Q et al.

Efficient fractionation of lignocellulosic components is a prerequisite for full-component utilization. Conventional methods rely on harsh conditions, causing severe degradation of cellulose and hemicellulose and lignin condensation, while milder conditions compromise fractionation efficiency. To balance native structure preservation and fractionation efficiency, a biphasic system composed of lithium bromide molten salt hydrate (MSH) and n-butanol was developed. At 110 °C for 1 h, cellulose and hemicellulose were selectively hydrolyzed into oligosaccharides in the MSH phase with yields of 81.4% and 88.1%, respectively. The isolated lignin retained 96.1% of β-O-4 ether bonds (38.5/100 C9 units), and its catalytic hydrogenolysis delivered a monophenol yield of 82.1% to the theoretical value. The light-colored lignin (ΔE = 31.28) achieved SPF 28.2 as a sole sunscreen active ingredient, demonstrating commercial potential. This biphasic system enables highly selective fractionation of lignocellulosic components with limited condensation, yielding key feedstocks for bioenergy and biorefinery, including oligosaccharides and native structure-preserved lignin.

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PubMedJournal of the American Chemical Society2026-07-27

Spin Manipulation Effect in Photodeprotection Reaction Using Triplet Ground-State Cation.

Takara Yugo Y, Takano Ma-Aya MA, Ishibashi Yukihide Y, Kishi Ryohei R et al.

Photolabile protecting groups (PPGs), which temporarily mask functional groups (LGs) and regenerate their activity upon light irradiation of PPG-LGs under reagent-free neutral conditions, have been widely utilized in diverse research fields ranging from organic synthesis to neuroscience. However, under conditions where diffusion of the ion pair consisting of PPG+ and LG- is unfavorable, the recombination reaction becomes dominant, making efficient photodeprotection difficult. If triplet ground-state cations could be generated, the recombination process would become spin-forbidden, thereby enhancing photodeprotection efficiency. As a proof of concept, we newly designed a PPG capable of generating the triplet ground-state cation 2-(4-methoxyphenyl)-1H-inden-1-ylium cation (T-PMI+). The generation process and dynamics of T-PMI+ were investigated by ultrafast transient absorption spectroscopy, while its reactivity was elucidated through chemical trapping experiments by benzyl bromide, molecular oxygen, and ferrocene. This study demonstrates spin manipulation as a new strategy for boosting the efficiency of photodeprotection reactions. Notably, a remarkably high deprotection selectivity of 92% was achieved.

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Exploring Tetrazolium Salt Reduction by Mono- and Bimetallic Nanoparticles as an Alternative Signal-Generation Strategy for Point-of-Care Diagnostics.

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Nanozymes, nanomaterials that mimic enzymatic activity, offer superior stability, tunability, and lower production costs compared to natural enzymes. To date, most nanozyme-based point-of-care (PoC) diagnostic systems have relied on oxidation reactions, such as oxidation of 3,3',5,5'-tetramethylbenzidine, which often suffer from limited substrate stability and high background signal. This study investigates reduction reactions, particularly those involving tetrazolium salts, as an alternative route for signal generation in PoC devices. For this purpose, monometallic and bimetallic gold, palladium, and platinum nanoparticles were synthesized via chemical reduction using poly(vinyl alcohol) as a stabilizing agent. The resulting nanoparticles were uniform in size and morphology. Their catalytic performance was confirmed through the reduction of 4-nitrophenol. The tetrazole salts were selected as promising substrates for application in PoC settings and further explored by examining the nanozyme-based reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The nanozymes catalyzed the reduction of MTT in the presence of sodium borohydride, producing a distinct colorimetric signal under selected conditions. The effects of reducing agent concentration, buffer pH, and potential interferents were evaluated, with performance suitable for PoC devices achieved at basic pH and low borohydride concentration. Interference studies showed negligible MTT reduction in the presence of physiological levels of ascorbic acid, human serum albumin, and 10% concentration of human serum. Finally, a proof-of-concept lateral flow assay demonstrated successful signal generation through nanozyme-catalyzed MTT reduction. Results establish tetrazolium salts as suitable substrates for nanozyme-enhanced PoC diagnostics and highlight reduction-based chromogenic systems as a viable alternative to traditional oxidation-based assays.

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The internalization of three types of carbon nanoparticles by HeLa cells in vitro.

Sun Lan L, Peng Fei F, Zhao Bao-Quan BQ, Zhang Hao H et al.

We have found activated carbon nanoparticles (ACNP) can be used as carriers of nanodrug delivery systems to treat cervical cancer. But how ACNP to enter into the HeLa cell, how to distribute, translocate and, metabolize and develop therapeutic effects has been unknown. In this paper, we invested the action of ACNP on HaLa cells in comparison with single walled carbon nanotubes (SWCNT) and quantum dots (QDs) in vitro. The effects of the nanoparticles on the HeLa cells were observed by tetrazolium bromide reduction (MTT) assay, lactate dehydrogenase leakage determination (LDH), flow cytometry, apoptotic rate, DNA comet assay. The morphological influences of nanoparticles on HeLa cells were observed with inverted microscope and atomic force microscopy (AFM); The mechanism of across cell membrane translocation of ACNP, SWCNT and QDs was investigated by treating the cells with endocytosis inhibitors and 4 °C low temperature. The three nanoparticles can inhibit the proliferation of HeLa cells in time- and concentration-dependent manners. Under the light microscope, the volume of HeLa cells treated by ACNP and SWCNT became smaller than that of control group. ACNP and SWCNT can induce HeLa cells shrinkage, weaken cell adhesion and increase the number of free cells in culture media. Under AFM, ACNP caused ill-defined cell membranes and membrane rupture; SWCNT caused cell shrinkage, reduced adhesion properties and "collapse-like" structure; QDs induced cell surface roughness and cell membrane folds. There are many irregular depressions in the cells. Flow cytometry showed that the three nanoparticles induced apoptosis of Hela cells. Electrophoresis showed the three nanoparticles induced DNA damage. Transmission electron microscopy(TEM) revealed that ACNP can pass through the cell membrane into the cytoplasm and further into the nucleus, causing disappearance of surface microvilli, mitochondrial swelling and nuclear shrinkage; SWCNT can enter into HeLa cells in the medium without inhibitors under room temperature, inducing cell and nuclear shrinkage, SWCNT was not found in the HeLa cells treated by inhibitors and low temperature; QDs was found accumulated in the cell membranes and can also cause swelling of mitochondria and increase cytoplasmic vacuoles. The three kinds of nanoparticles can inhibit the growth and cause apoptosis of HeLa cells; the mechanism may be nuclear DNA damage and increased membrane permeability; The internalization of SWCNT by HeLa cells is energy dependent while the internalization of ACNP is independent of energy. The DNA damage effects of ACNP may be realized through two ways, one of which is to injure cell membranes and the other is to act on DNA directly. QDs damage DNA mainly through the action of cell membranes.

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In situ formation of deep eutectic solvent for disperser-free microextraction of Fast Green and Erythrosine in food and pharmaceutical samples.

Abdelwahed Fatma T FT, Mortada Wael I WI, Hassan Nourhan N NN, Eltabey Rania M RM

A rapid, environmentally friendly, in situ deep eutectic solvent (DES) based liquid-liquid microextraction method was proposed for the preconcentration and determination of Fast Green (FG) and Erythrosine (ER) in food and pharmaceutical samples. The DES, which was synthesized in situ without the need for disperser liquids or prior preparation, was composed of thymol and tetrabutylammonium bromide (1:2). Key extraction parameters, including pH, DES ratio, extraction time, temperature, ionic strength, and centrifugation time, were adjusted to achieve maximum efficiency. The interaction mechanism between the dyes and DES was investigated using FT-IR and UV-Visible spectroscopy. Under optimal conditions, the method showed good linearity over 30-1200 µg L⁻¹ for FG and 48-2000 µg L⁻¹ for ER, with detection limits of 9.0 and 13.9 µg L⁻¹ for FG and ER, respectively. The method exhibited high precision (RSD < 4%) and satisfactory recoveries (97.5-99.9%) in spiked samples. Greenness assessment and applicability of the method were assessed using AGREEprep and Click Analytical Chemistry Index tools.

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Berberine Enhancement of Clarithromycin Activity Against Mycobacterium abscessus: A Correlation with Suppression of Inducible Resistance and Efflux Pumps.

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Rising clarithromycin (CLA) resistance complicates Mycobacterium abscessus (MAB) treatment. We evaluated berberine (BER) as a CLA adjuvant and explored factors potentially associated with its effect. Thirty MAB strains (29 clinical isolates with varying CLA susceptibility and ATCC 19977) were analyzed. Synergistic interactions were quantified via checkerboard and expressed as the fractional inhibitory concentration index (FICI), with time-kill kinetics for bactericidal activity. Gene expression (RT-qPCR), efflux pump activity (ethidium bromide accumulation), and biofilm inhibition were assessed. BER-CLA showed additive-to-synergistic effects (FICI ≤1) in all strains, reducing CLA MIC by ≥4-fold in 60.0% of isolates and achieving the susceptible breakpoint (≤2 µg/mL) in 61.1% of non-susceptible strains. A trend toward genotype-associated synergy appeared: all wild-type rrl or non-2269-2271 mutants showed synergy/partial synergy, versus only 50.0% of 2269-2271 mutants. BER transiently suppressed CLA-induced resistance genes (whiB7, erm(41), hflX) in non-A2270G mutants at early time points (1-3 h), but this effect waned at 24-48 h. It also downregulated efflux pump genes (MAB_2355c, MAB_1409c) and partially inhibited efflux activity. These findings suggest that BER potentiates CLA in association with suppression of inducible resistance and efflux, rather than acting via constitutive ribosomal mutations. Additionally, BER-CLA modestly reduced biofilm formation (P < 0.05), suggesting complementary benefit. BER appears to be a promising adjuvant for CLA treatment of MAB, with a trend toward enhanced activity in wild-type rrl strains and those without 2269-2271 mutations. These findings support developing BER-based strategies against CLA resistance, potentially in association with modulating inducible resistance.

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