更新于：2024-11-21

Malotilate

马洛替酯

更新于：2024-11-21

概要

概要

基本信息

药物类型

小分子化药

别名

Malotilate (JAN/USAN/INN)

+ [4]

靶点-

作用机制-

治疗领域

消化系统疾病血液及淋巴系统疾病

在研适应症

低蛋白血症肝病

非在研适应症-

原研机构-

在研机构-

非在研机构-

最高研发阶段批准上市

首次获批日期

(1985-01-01),

低蛋白血症肝病

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C12H16O4S2

InChIKeyYPIQVCUJEKAZCP-UHFFFAOYSA-N

CAS号59937-28-9

关联

100 项与马洛替酯相关的临床结果

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100 项与马洛替酯相关的转化医学

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100 项与马洛替酯相关的专利（医药）

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项与马洛替酯相关的文献（医药）

2022-12-01·Journal of Cachexia, Sarcopenia and Muscle

Inhibiting 5‐lipoxygenase prevents skeletal muscle atrophy by targeting organogenesis signalling and insulin‐like growth factor‐1

Article

作者: Jung, Da‐Woon ; Lee, Sang‐Hoon ; Kim, Seon‐Wook ; Kim, Hyun‐Jun ; Williams, Darren R.

AbstractBackgroundSkeletal muscle atrophy can occur in response to numerous factors, such as ageing and certain medications, and produces a major socio‐economic burden. At present, there are no approved drugs for treating skeletal muscle atrophy. Arachidonate 5‐lipoxygenase (Alox5) is a drug target for a number of diseases. However, pharmacological targeting of Alox5, and its role in skeletal muscle atrophy, is unclear.MethodsThe potential effects of gene knockdown and pharmacological targeting of Alox5 on skeletal muscle atrophy were investigated using cell‐based models, animal models and human skeletal muscle primary cells. Malotilate, a clinically safe drug developed for enhancing liver regeneration and Alox5 inhibitor, was investigated as a repurposing candidate. Mechanism(s) of action in skeletal muscle atrophy was assessed by measuring the expression level or activation status of key regulatory pathways and validated using gene knockdown and RNA sequencing.ResultsMyotubes treated with the atrophy‐inducing glucocorticoid, dexamethasone, were protected from catabolic responses by treatment with malotilate (+41.29%, P < 0.01). Similar anti‐atrophy effects were achieved by gene knockdown of Alox5 (+30.4%, P < 0.05). Malotilate produced anti‐atrophy effects without affecting the myogenic differentiation programme. In an in vivo model of skeletal muscle atrophy, malotilate treatment preserved muscle force/strength (grip strength: +35.72%, latency to fall: +553.1%, P < 0.05), increased mass and fibre cross‐sectional area (quadriceps: +23.72%, soleus: +33.3%, P < 0.01) and down‐regulated atrogene expression (Atrogin‐1: −61.58%, Murf‐1: ‐66.06%, P < 0.01). Similar, beneficial effects of malotilate treatment were observed in an ageing muscle model, which also showed the preservation of fast‐twitch fibres (Type 2a: +56.48%, Type 2b: +37.32%, P < 0.01). Leukotriene B4, a product of Alox5 activity with inflammatory and catabolic functions, was found to be elevated in skeletal muscle undergoing atrophy (quadriceps: +224.4%, P < 0.001). Cellular transcriptome analysis showed that targeting Alox5 up‐regulated biological processes regulating organogenesis and increased the expression of insulin‐like growth factor‐1, a key anti‐atrophy hormone (+226.5%, P < 0.05). Interestingly, these effects were restricted to the atrophy condition and not observed in normal skeletal muscle cultures with Alox5 inhibition. Human myotubes were also protected from atrophy by pharmacological targeting of Alox5 (+23.68%, P < 0.05).ConclusionsThese results shed new light on novel drug targets and mechanisms underpinning skeletal muscle atrophy. Alox5 is a regulator and drug target for muscle atrophy, and malotilate is an attractive compound for repurposing studies to treat this disease.

2011-07-01·International Journal of Pharmaceutics2区 · 医学

Physicochemical and pharmacokinetic characterization of a spray-dried malotilate emulsion

2区 · 医学

Article

作者: Hui Zu ; Jianjun Zhang ; Yuan Gao ; Xin Liu ; Shuai Qian

Malotilate (MT) is a hepatoprotective drug administered orally. However, MT was found to be a poorly water-soluble drug with low oral bioavailability. In the present investigation, a novel spray-dried emulsion (SDE) loaded with MT was prepared, and its physicochemical properties were characterized by rheological evaluation, particle size measurement, in vitro release, and surface morphology. The pharmacokinetic study of SDE, in comparison to MT suspension with the pure MT powder homogeneously dispersed in 0.5% CMC-Na solution, was also performed in rats after a single oral dose. It was found that SDE exhibited a 2.9-fold higher peak plasma concentration (C(max)) and 2.3-fold higher area under the curve (AUC) than MT suspension.

2003-08-01·Journal of Hepatology1区 · 医学

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

1区 · 医学

Article

作者: Erik Christensen ; Ulrik Becker ; Lene Theil Skovgaard ; Julia S Johansen ; Paul A Price ; Camilla Nøjgaard

BACKGROUND/AIMSYKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease.METHODSThree hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA).RESULTSSerum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004).CONCLUSIONSSerum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.

100 项与马洛替酯相关的药物交易

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