Macozinone(Macozinone) - 药物靶点：DprE1_在研适应症：肺结核，结核_专利_临床

概要

基本信息

药物类型

小分子化药

别名

MCZ

+ [2]

靶点

DprE1

作用方式

抑制剂

作用机制

DprE1抑制剂(FAD依赖性十聚丙烯基磷酰基-β-D-呋喃核糖二氧化酶抑制剂)

治疗领域

感染呼吸系统疾病

在研适应症

肺结核结核

非在研适应症-

原研机构

École Polytechnique Fédérale de Lausanne

在研机构

Chemical Diversity Research Institute CJSCNearmedic Pharma Ltd.

École Polytechnique Fédérale de Lausanne

非在研机构

Nearmedic Plus Ltd.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C20H23F3N4O3S

InChIKeyBJDZBXGJNBMCAV-UHFFFAOYSA-N

CAS号1377239-83-2

关联

5

项与 Macozinone 相关的临床试验

NCT03776500

/ Completed临床1期

Safety, Tolerability and Pharmacokinetic Profile of PBTZ169 Formulated as Native Crystal Powder: Multiple Ascending Doses, Randomized, Placebo- Controlled, Parallel-group, Sequential Phase Ib Trial in Healthy Volunteers

This is a randomized, double-blind, placebo-controlled, multiple ascending dose study conducted at one study center in Switzerland.
Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each receiving multiple doses of PBTZ169 or a matching placebo, at increasing dose levels, once or twice daily.
Subjects will participate in only one panel. Blocks of 4 subjects (3 under active treatment, 1 under placebo) will be investigated in parallel. Panels will start sequentially.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of PBTZ169.
Dose escalation will be allowed once the Trial Safety Board has determined that adequate safety and tolerability after each panel completion has been demonstrated to permit proceeding to the next panel.
In addition, a preliminary assessment of the drug interaction potential of PBTZ169 will be done by the measurement of inhibition or induction of human cytochromes through the metabolism of microdoses of standard probe substrates

开始日期2019-02-21

申办/合作机构

Pioneering Medicines

[+1]

NCT04150224

/ Completed临床1期

An Open-label, Prospective Study of Safety, Tolerability, Pharmacokinetics and Food Effects of PBTZ169, 80 mg Capsules, When Used in Ascending Doses in Healthy Volunteers

Open-label prospective non-comparative ascending dose randomized cohort study of single and multiple oral administration of PBTZ169 (capsules 80 mg) in healthy volunteers

开始日期2018-07-03

申办/合作机构

Nearmedic Plus Ltd.

NCT03423030

/ Completed临床1期

Safety, Tolerability, Pharmacokinetic Profile and Ex-vivo Antitubercular Activity of PBTZ169 Formulated as Spray- Dried Dispersion Versus Native Crystal Powder: Single Ascending Doses, Randomized, Placebo- Controlled, Cross-over Phase Ia Trial in Healthy Volunteers

This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in Switzerland.
Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each undergoing 2 investigation periods and receiving either single doses of PBTZ169 at increasing dose levels or a matching placebo.
Subjects will participate in only one panel. Blocks of 4 subjects (3 under active treatment, 1 under placebo) will be investigated in parallel. Panels A and B are interleaved.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of PBTZ169.
Dose escalation will be allowed once the Trial Safety Board has determined that adequate safety and tolerability after panel B and panel C completion has been demonstrated to permit proceeding to the next panel.

开始日期2017-12-05

申办/合作机构

Pioneering Medicines

[+1]

100 项与 Macozinone 相关的临床结果

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100 项与 Macozinone 相关的转化医学

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100 项与 Macozinone 相关的专利（医药）

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211

项与 Macozinone 相关的文献（医药）

2025-05-01·Talanta

Exploring wood-derived biochar potential for electrochemical sensing of fungicides mancozeb and maneb in environmental water samples

Article

作者: Anojčić, Jasmina ; Petrović, Jelena ; Apostolović, Tamara ; Mutić, Sanja ; Beljin, Jelena ; Đukanović, Nina ; Simetić, Tajana

The sustainable material, biochar (BC) from a hardwood source, was synthesized via pyrolysis process at 400 °C (BC400) and 700 °C (BC700) and used as a modifier during the electrochemical sensor design. The prepared BCs were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, and elemental analysis (CHNS). The development of rapid analytical techniques for detecting pesticides employing a low-cost carbon paste electrode (CPE) modified with BC is a novel strategy to provide a sensitive response to water pollution. The prepared working electrodes (unmodified CPE, BC400-CPE, and BC700-CPE) were compared for selected fungicides mancozeb (MCZ) and maneb (MAN) sensing, and BC700-CPE provides the most favorable analytical response of target analytes. Cyclic voltammetric investigations revealed that the electrode reaction is irreversible and controlled by the adsorption of MCZ and MAN at the surface of the BC700-CPE, which led to an optimization of the differential pulse adsorptive stripping voltammetric (DP-AdSV) method. The obtained working linear concentration ranges were 25-2780 μg L^-1 MCZ and 49-1840 μg L^-1 MAN in Britton-Robinson buffer pH 7.0 using CPE modified with 10 % BC700. The evaluated limit of detection was 7.5 μg L^-1 for MCZ and 15.0 μg L^-1 for MAN. Investigated interferences did not significantly affect the MCZ and MAN oxidation signal intensity. The developed DP-AdSV method was successfully applied to determine selected fungicides in spiked river water and wastewater samples, with good recovery and reproducibility.

2025-04-01·European Journal of Pharmacology

Biochemical insights into synergistic Candida biofilm disintegrating ability of p-cymene inclusion complex and miconazole

Article

作者: Yadav, Bhawana ; Poluri, Krishna Mohan ; Kumar, Amit ; Mishra, Purusottam ; Roy, Ankita ; Gupta, Payal

Phytoactive molecules emerge as a plentiful reservoir of adjuvant and antifungal agents. The resolution of solubility and stability issues has been facilitated by developing molecular complexes or inclusion complexes of phytoactive molecules. Miconazole (MCZ) is a favoured azole with low off-target impact, however, its pharmacological efficacy requires a revamp to enhance its suitability as an antifungal drug. Hence, the present investigation delves into the mechanism of action of the p-cymene/β-cyclodextrin inclusion complex (IC) along with MCZ against Candida albicans and Candidaglabrata biofilms. The synergy between IC and MCZ has been estimated at a concentration of 6.25 μg/mL IC + 0.5 μg/mL MCZ with a FICI of 0.19. The prepared IC + MCZ displayed remarkable antifungal properties against planktonic and sessile growth of Candida species. IC + MCZ exhibited a notable 80% biofilm eradication potential against both species, corroborated by morphological analysis using FE-SEM. The results indicated that IC/IC + MCZ acts by disrupting the biochemical composition of the ECM, altering the surface properties of the cells, reducing ergosterol, enhancing membrane permeability, and inducing oxidative stress. In conclusion, the study highlighted the synergistic antibiofilm activity of p-cymene IC with miconazole against Candida species. In summary, IC + MCZ has been established as a potent antifouling agent against Candida species, warranting further exploration for potential formulation with additional investigations.

2025-04-01·Chemosphere

Mancozeb exposure disrupts endocrine function of the ovary and thyroid in Red Munia (Amandava amandava)

Article

作者: Mohanty, Banalata

Mancozeb (MCZ), a dithiocarbamate fungicide, has the potential to disrupt thyroid hormone (TH) functioning in non-target organisms. THs play a crucial role in seasonal reproduction and previous studies have shown that even low levels of MCZ exposure can affect thyroid and testicular function in the Red Munia bird (Amandava amandava), a distinct seasonal breeder. This study specifically examines the impact of MCZ exposure on female Red Munia to investigate any sex-specific effects. Exposure to sublethal levels (0.5% LD50) of MCZ for 30 consecutive days during the critical transition to the breeding phase disrupts the pituitary-ovarian and pituitary-thyroid axes in Red Munia. The morphometry (number/size/immunointensity) of pituitary luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) producing cells, immunoreacted with anti-human (h) LHβ/anti-chicken (c) LHβ, and anti-hTSH β respectively, was significantly altered. Plasma levels of LH (p < 0.01), follicle-stimulating hormone (p < 0.001), and TSH (p < 0.01) were significantly decreased. There was a significant increase in the number of atretic primordial and primary follicles, thinning and disorganization of the granulosa cell layers in maturing follicles, and significant decrease in plasma levels of estradiol (p < 0.001).The reduced diameter of the thyroid gland, a significant increase in empty follicles, and a decrease in plasma levels of THs (T3, p < 0.01; T4, p < 0.001), indicate disruption of thyroid function. It is not only MCZ and its residual products, but also the inert ingredients in the commercial formulation/metabolites, may have contributed to the interference with thyroid function during the transition to the breeding phase to compromise ovarian recrudescence in the Red Munia bird.

100 项与 Macozinone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14821

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肺结核	临床2期	-	École Polytechnique Fédérale de Lausanne	-
结核	临床前	俄罗斯	Chemical Diversity Research Institute CJSC	2022-11-14
结核	临床前	俄罗斯	Nearmedic Pharma Ltd.	2022-11-14

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03036163 (CTgov)	临床1期	结核	40	PBTZ169 - 40 mg (Cohort 1)	範願鏇鹽膚襯衊築鏇築(衊鹹醖艱壓夢構艱憲襯) = 餘壓鏇淵願夢蓋構膚獵構獵醖窪鏇壓淵襯築願 (製顧廠範鹽膚構夢製壓, 觸獵獵齋範繭顧膚糧鹹 ~ 願遞衊艱遞遞繭製夢艱) 更多	-	2020-04-13
				PBTZ169 - 80 mg (Cohort 2)	範願鏇鹽膚襯衊築鏇築(衊鹹醖艱壓夢構艱憲襯) = 鑰鏇範廠簾範艱製糧齋構獵醖窪鏇壓淵襯築願 (製顧廠範鹽膚構夢製壓, 築壓範襯艱壓獵觸範鏇 ~ 遞構鏇壓襯觸廠願壓窪) 更多
NCT03334734 (CTgov)	临床2期	肺结核	16	PBTZ169 (PBTZ169, 160 mg)	(構糧製齋製夢顧鏇網淵) = 範鬱願構壓蓋衊壓壓淵網選衊淵蓋壓願遞製窪 (簾繭鹽築網憲糧窪蓋鬱, 鏇積淵網遞醖淵鏇襯製 ~ 膚鹽築獵蓋積壓鏇遞糧) 更多	-	2020-03-09
				PBTZ169 (PBTZ169, 320 mg)	(構糧製齋製夢顧鏇網淵) = 餘願夢觸壓遞夢選願窪網選衊淵蓋壓願遞製窪 (簾繭鹽築網憲糧窪蓋鬱, 襯蓋衊艱願鬱齋淵蓋憲 ~ 窪願壓鬱襯鏇遞膚糧鏇) 更多
NCT04150224 (CTgov)	临床1期	-	60	PBTZ169 960 mg SD (Cohort 2 (C2), PBTZ169)	夢築鑰膚築廠簾鹹憲夢(築壓齋願鏇鑰選艱鹽選) = 廠糧衊膚淵鹹鏇艱鑰鏇築餘鬱鹽蓋艱廠廠遞繭 (鹹築鏇衊鏇窪鬱壓淵壓, 選餘築蓋壓製獵築糧願 ~ 蓋選構憲餘繭遞願製齋) 更多	-	2020-02-28
				PBTZ169 640 mg BiD (Cohort 3 (C3), PBTZ169)	夢築鑰膚築廠簾鹹憲夢(築壓齋願鏇鑰選艱鹽選) = 鬱築餘鑰淵餘襯齋廠醖築餘鬱鹽蓋艱廠廠遞繭 (鹹築鏇衊鏇窪鬱壓淵壓, 製築獵壓蓋廠網衊顧窪 ~ 鬱簾遞衊簾構遞壓觸鏇) 更多