青蒿琥酯/乙胺嘧啶/磺胺林(Artesunate/Pyrimethamine/Sulfalene) - 药物靶点：ATP2A1 x DHFR x DHPS x SERCA2_在研适应症：疟疾_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AS/SP、Co-Arinate、Coarinate

靶点

ATP2A1 x DHFR x DHPS x SERCA2

作用机制

ATP2A1抑制剂(肌浆网/内质网钙ATP酶-1抑制剂)、DHFR抑制剂(二氢叶酸还原酶抑制剂)、DHPS抑制剂(二氢叶酸合成酶抑制剂)

治疗领域

感染

在研适应症

疟疾

非在研适应症-

原研机构

Dafra Pharma NV

在研机构

Dafra Pharma NV

非在研机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C11H12N4O3S

InChIKeyKXRZBTAEDBELFD-UHFFFAOYSA-N

CAS号152-47-6

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关联

11

项与青蒿琥酯/乙胺嘧啶/磺胺林相关的临床试验

NCT00510159 / Completed临床2/3期

Randomized Double Blind Clinical Trial in Mali, Comparing the Effectiveness of Artesunate + Sulfamethoxypyrazine/Pyrimethamine Versus Praziquantel in the Treatment of S. Haematobium in Children

The purpose of this study is to evaluate the efficacy of praziquantel versus As+SMP (Co-Arinate FDC ®) in the treatment of Schistosoma haematobium in 6-15 year old Malian children. The nul-hypothesis in this study is that the combination of As+SMP is more effective than praziquantel in the treatment of S. haematobium infected children.

开始日期2007-08-01

申办/合作机构

Dafra Pharma NV

NCT00484900 / Completed临床3期

Open Randomized Multi-Centre Trial, Comparing Artesunate-Sulfamethoxypyrazine-Pyrimethamine FDC Over 3 Days, Artesunate-Sulfamethoxypyrazine-Pyrimethamine FDC Over 48 Hours and Artemether-Lumefantrine FDC Over 3 Days on P. Falciparum Malaria

The purpose of this open randomised multi-centre clinical trial is to test the hypothesis that three pills of the fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine, administered over 24 hours is not inferior in efficacy to the same drug administered over 48 hours and that the fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine As/SMP fdc, independently of the duration of its dose interval, is not inferior in efficacy to 6 - 24 pills (number of pills administered to respectively children and adults)of the 60 hours treatment of artemether/lumefantrine for the treatment of uncomplicated P. falciparum malaria.

开始日期2006-05-01

申办/合作机构

Dafra Pharma NV

NCT00127998 / CompletedN/AIIT

Characterization of Novel Molecular Tools for the Epidemiological Surveillance of Antimalarial Drug Resistance in Mali

Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to:
Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested.
Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria
Measure drug levels at 3 days and correlate with efficacy results.
Examine early clinical, parasitologic, and clinical predictors of late treatment failure.
Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.

开始日期2005-07-01

申办/合作机构

Centers for Disease Control & Prevention

100 项与青蒿琥酯/乙胺嘧啶/磺胺林相关的临床结果

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100 项与青蒿琥酯/乙胺嘧啶/磺胺林相关的转化医学

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100 项与青蒿琥酯/乙胺嘧啶/磺胺林相关的专利（医药）

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27

项与青蒿琥酯/乙胺嘧啶/磺胺林相关的文献（医药）

2019-07-01·Journal of helminthology

Efficacy of artemisinin–naphthoquine phosphate against Schistosoma haematobium adult flukes: dose–effect relationship and tegumental alterations

Article

作者: Taman, A ; El-Beshbishi, S N ; Ayoub, M ; Tadros, M ; El Bardicy, S

Abstract:

Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin–naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1–40 μg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 μg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin–naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.

2019-06-01·Transactions of the Royal Society of Tropical Medicine and Hygiene4区 · 医学

Biological activity of artemisinin-naphthoquine phosphate on Schistosoma haematobium stages and the vector Bulinus truncatus

4区 · 医学

Article

作者: El-Beshbishi, Samar N ; El Bardicy, Samia ; Taman, Amira ; Ayoub, Magda ; Tadros, Menerva

BACKGROUND:

Schistosoma haematobium infection is a major public health problem in most of Africa and the Middle East and praziquantel remains the only drug used for schistosomiasis control, therefore emergence of drug resistance is unavoidable. The antimalarial artemisinin-naphthoquine phosphate combination (co-ArNp) was recently documented to have promising effects on Schistosoma mansoni and its snail host.

METHODS:

We conducted this in vitro study to assess the bioactivity of co-ArNp on S. haematobium and its snail vector Bulinus truncatus.

RESULTS:

Treatment of S. haematobium worms with 1 μg/ml co-ArNp for 24 h reduced worm motility, while 20 μg/ml resulted in 25-100% mortality of adult flukes within 48-72 h. Incubation of S. haematobium miracidia and cercariae with the molluscicidal co-ArNp (50% lethal concentration 7.5 μg/ml) killed all the free larval stages within 40 and 15 min, respectively. Also, exposure of B. truncatus adult snails to 20 ppm of the combined regimen caused a mortality rate of 100% within 24 h.

CONCLUSIONS:

Co-ArNp therapy has also shown encouraging activity against the other major human schistosome, S. haematobium, as well as its vector.

2018-09-01·Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases3区 · 医学

Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicated Plasmodium falciparum malaria cases along international border of north east India

3区 · 医学

Article

作者: Valecha, Neena ; Yadav, Chander Prakash ; Goomber, Shelly ; Anvikar, Anup ; Mishra, Neelima

PfMDR1 single nucleotide polymorphisms (SNP) are good correlate markers for antimalarial drug resistance worldwide. Present study is a comprehensive view of screening of PfMDR1 polymorphism to antimalarials practiced with geography and time. Study sites Mizoram, Tripura, Meghalaya chosen are at multivariate drug pressure due to cross border migration and transmission. Mizoram is gateway to south east Asia through Myanmar whereas Tripura, Meghalaya share porous border with Bangladesh. Baseline finger pricked blood stained filter paper for confirmed uncomplicated Plasmodium falciparum infected patients (year 2015) were obtained from National Institute of Malaria Research, New Delhi, India. PfMDR1 polymorphism for codon N86Y, Y184F, D1246Y was determined by PCR-RFLP, further confirmed by sequencing. There observed marked predominance of Plasmodium isolates with PfMDR1 wild type alleles for all codons under study i.e. 86, 184, 1246. Spatially, Plasmodium isolates from Mizoram were most diverse with co-existence of PfMDR1 genotype with NYD, YYD, NFD haplotypes, followed by Tripura. Isolates from Meghalaya were of all NYD haplotype. Reports, referring to screening of PfMDR1 SNPs to CQ/SP/AS-SP across India, were archived. Temporal study show distinct rise in proportion of PfMDR1 wild type N86 allele since introduction of Artemether-Lumefantrine as first line antimalarial. Hence spatio-temporal screening of Plasmodium population with PfMDR1 single nucleotide polymorphism accounts for its association with antimalarial susceptibility and validate PfMDR1 SNPs as antimalarial drug resistant marker.

100 项与青蒿琥酯/乙胺嘧啶/磺胺林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
疟疾	-	Dafra Pharma NV	-

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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


NCT00484900 (Pubmed \| Malar J)	临床3期	恶性疟	1,390	artesunate-sulphamethoxypyrazine-pyrimethamine three-day regimen	觸築醖獵築夢製願醖廠(廠憲衊選淵鹽遞鑰鹽膚) = 簾鏇鏇範觸繭憲淵衊簾齋遞壓積製簾網齋積簾 (齋鹽淵鏇顧窪獵鏇製鏇 )	-	2009-04-14
				artesunate-sulphamethoxypyrazine-pyrimethamine 24-hour regimen	觸築醖獵築夢製願醖廠(廠憲衊選淵鹽遞鑰鹽膚) = 齋憲簾繭膚艱範鑰網鬱齋遞壓積製簾網齋積簾 (齋鹽淵鏇顧窪獵鏇製鏇 )