AQ-13(AQ-13) - _专利_临床

概要

基本信息

药物类型

小分子化药

别名

Aminoquinolone-13

靶点-

作用方式-

作用机制-

治疗领域

感染

在研适应症-

非在研适应症

疟疾

原研机构

Immtech Pharmaceuticals, Inc.

在研机构-

非在研机构

Immtech Pharmaceuticals, Inc.

权益机构-

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构/序列

分子式C16H22ClN3

InChIKeyNCPLTAGJJVCHOW-UHFFFAOYSA-N

CAS号32571-49-6

关联

3

项与 AQ-13 相关的临床试验

NCT01614964

/ Completed临床2期

Phase 2 Proof of Concept Study of a Candidate Aminoquinoline Antimalarial (AQ-13)

This is an initial efficacy study of a candidate antimalarial in human subjects with uncomplicated malaria caused by the most common and most important parasite in Africa (Plasmodium falciparum). This study will enroll 66 adult Malian males with uncomplicated P. falciparum malaria and randomize them to treatment with 1750 mg of the investigational drug (AQ-13) by mouth over 3 days or the current standard treatment, which is 2 doses of Coartem twice daily for 3 days. The hypothesis underlying this study is that AQ-13 will be similarly effective to Coartem for the treatment of uncomplicated P. falciparum malaria due to both chloroquine-susceptible and chloroquine-resistant parasites. Funding Source - FDA Office of Orphan Product Development (OOPD).

开始日期2013-08-01

申办/合作机构

University of Bamako

NCT00455494

/ Completed临床1期IIT

Food-Effect Bioavailability Study of AQ-13, a Candidate Antimalarial

The purpose of this study is to test the safety of a 2100 mg dose of AQ-13, a new candidate antimalarial active against drug-resistant P. falciparum infection, and to determine the effect of a standard fatty meal on the absorption of the drug from the gut and its blood levels.

开始日期2005-01-01

申办/合作机构

Tulane University Health Sciences Center

[+1]

NCT00323375

/ Completed临床1期IIT

Randomized Controlled Trial of AQ-13, a Candidate Aminoquinoline Antimalarial, in Comparison With Chloroquine

The purpose of this protocol is to perform Phase 1 (safety/toxicity and pharmacokinetic) Studies of an investigational aminoquinoline antimalarial (AQ-13) in human subjects. The compound to be studied (AQ-13) is being examined because it is active in vitro against Plasmodium falciparum malaria parasites resistant to chloroquine (CQ) and other antimalarials (multi-resistant P. falciparum), and because its safety was similar to that of CQ in preclinical studies performed by SRI International (IND 55,670). AQ-13 was also selected for study because it is active in vivo in two monkey models of human malaria: 1] P. cynomolgi in the rhesus monkey (Macaca mulatta), a model of human infection with P. vivax, and 2] CQ-resistant P. falciparum in the squirrel monkey, a model of human infection with CQ-resistant P. falciparum.

开始日期1999-08-01

申办/合作机构

Tulane University Health Sciences Center

[+1]

100 项与 AQ-13 相关的临床结果

登录后查看更多信息

100 项与 AQ-13 相关的转化医学

登录后查看更多信息

100 项与 AQ-13 相关的专利（医药）

登录后查看更多信息

26

项与 AQ-13 相关的文献（医药）

2021-09-15·Journal of Antimicrobial Chemotherapy2区 · 医学

Cross-resistance of the chloroquine-derivative AQ-13 with amodiaquine in Cambodian Plasmodium falciparum isolates

2区 · 医学

Article

作者: Nardella, Flore ; Mairet-Khedim, Mélissa ; Leroy, Didier ; Leang, Rithea ; Ke, Sopheakvatey ; Witkowski, Benoit ; Maher, Steven P ; Roesch, Camille

AbstractBackgroundExpanding resistance to multiple antimalarials, including chloroquine, in South-East Asia (SEA) urges the development of new therapies. AQ-13, a chloroquine derivative, is a new drug candidate for treating malaria caused by Plasmodium falciparum.ObjectivesPossible cross-resistance between the 4-aminoquinolines amodiaquine, piperaquine and AQ-13 has not been assessed. In vitro parasite growth assays were used to characterize the susceptibility of multidrug-resistant and susceptible P. falciparum patient isolates to AQ-13.MethodsA [3H]hypoxanthine uptake assay and a 384-well high content imaging assay were used to assess efficacy of AQ-13 and desethyl-amodiaquine against 38 P. falciparum isolates.ResultsWe observed a strong cross-resistance between the chloroquine derivative amodiaquine and AQ-13 in Cambodian P. falciparum isolates (Pearson correlation coefficient of 0.8621, P < 0.0001).ConclusionsIn light of the poor efficacy of amodiaquine that we described recently in Cambodia, and its cross resistance with AQ-13, there is a significant risk that similar clinical efficacy of AQ-13-based combinations should be anticipated in areas of amodiaquine resistance.

2021-09-01·The Lancet Microbe

Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study

Article

作者: Bayles, Brett R ; Ceja, Frida G ; Rosenthal, Philip J ; Bailey, Jeffrey A ; Asua, Victor ; Chelebieva, Sevil ; Tumwebaze, Patrick K ; Duvalsaint, Marvin ; Nsobya, Samuel L ; Rasmussen, Stephanie A ; Byaruhanga, Oswald ; Legac, Jennifer ; Orena, Stephen ; Okitwi, Martin ; Conrad, Melissa D ; Katairo, Thomas ; Cooper, Roland A ; Aydemir, Ozkan

BACKGROUNDTreatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda.METHODSIn this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda with clinical symptoms of malaria, a positive Giemsa-stained blood film for P falciparum, and no signs of severe disease. Ex-vivo susceptibilities to ten antimalarial drugs were measured using a 72-h microplate growth inhibition assay with SYBR Green detection. Relevant P falciparum genetic polymorphisms were characterised by molecular methods. We compared results with those from earlier studies in this region and searched for associations between drug susceptibility and parasite genotypes.FINDINGSFrom June 10, 2016, to July 29, 2019, 361 P falciparum isolates were collected in the Busia district and 79 in the Tororo district from 440 participants. Of 440 total isolates, 392 (89%) successfully grew in culture and showed excellent drug susceptibility for chloroquine (median half-maximal inhibitory concentration [IC₅₀] 20·0 nM [IQR 12·0-26·0]), monodesethylamodiaquine (7·1 nM [4·3-8·9]), pyronaridine (1·1 nM [0·7-2·3]), piperaquine (5·6 nM [3·3-8·6]), ferroquine (1·8 nM [1·5-3·3]), AQ-13 (24·0 nM [17·0-32·0]), lumefantrine (5·1 nM [3·2-7·7]), mefloquine (9·5 nM [6·6-13·0]), dihydroartemisinin (1·5 nM [1·0-2·0]), and atovaquone (0·3 nM [0·2-0·4]). Compared with results from our study in 2010-13, significant improvements in susceptibility were seen for chloroquine (median IC₅₀ 288·0 nM [IQR 122·0-607·0]; p<0·0001), monodesethylamodiaquine (76·0 nM [44·0-137]; p<0·0001), and piperaquine (21·0 nM [7·6-43·0]; p<0·0001), a small but significant decrease in susceptibility was seen for lumefantrine (3·0 nM [1·1-7·6]; p<0·0001), and no change in susceptibility was seen with dihydroartemisinin (1·3 nM [0·8-2·5]; p=0·64). Chloroquine resistance (IC₅₀>100 nM) was more common in isolates from the Tororo district (11 [15%] of 71), compared with those from the Busia district (12 [4%] of 320; p=0·0017). We showed significant increases between 2010-12 and 2016-19 in the prevalences of wild-type P falciparum multidrug resistance protein 1 (PfMDR1) Asn86Tyr from 60% (391 of 653) to 99% (418 of 422; p<0·0001), PfMDR1 Asp1246Tyr from 60% (390 of 650) to 90% (371 of 419; p<0·0001), and P falciparum chloroquine resistance transporter (PfCRT) Lys76Thr from 7% (44 of 675) to 87% (364 of 417; p<0·0001).INTERPRETATIONOur results show marked changes in P falciparum drug susceptibility phenotypes and genotypes in Uganda during the past decade. These results suggest that additional changes will be seen over time and continued surveillance of susceptibility to key ACT components is warranted.FUNDINGNational Institutes of Health and Medicines for Malaria Venture.

2020-11-06·Journal of Proteome Research2区 · 生物学

Theoretical Insights into the Anti-SARS-CoV-2 Activity of Chloroquine and Its Analogs and In Silico Screening of Main Protease Inhibitors

2区 · 生物学

Article

作者: Pushpa, V. L. ; Achutha, A. S. ; Suchitra, Surendran

Corona virus disease (COVID-19) is a dangerous disease rapidly spreading all over the world today. Currently there are no treatment options for it. Drug repurposing studies explored the potency of antimalarial drugs, chloroquine and hydroxychloroquine, against SARS-CoV-2 virus. These drugs can inhibit the viral protease, called chymotrypsin-like cysteine protease, also known as Main protease (3CL^pro); hence, we studied the binding efficiencies of 4-aminoquinoline and 8-aminoquinoline analogs of chloroquine. Six compounds furnished better binding energies than chloroquine and hydroxychloroquine. The interactions with the active site residues especially with Cys145 and His41, which are involved in catalytic diad for proteolysis, make these compounds potent main protease inhibitors. A regression model correlating binding energy and the molecular descriptors for chloroquine analogs was generated with R² = 0.9039 and Q² = 0.8848. This model was used to screen new analogs of primaquine and molecules from the Asinex compound library. The docking and regression analysis showed these analogs to be more potent inhibitors of 3CL^pro than hydroxychloroquine and primaquine. The molecular dynamic simulations of the hits were carried out to determine the binding stabilities. Finally, we propose four compounds that show drug likeness toward SARS-CoV-2 that can be further validated through in vitro and in vivo studies.

100 项与 AQ-13 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
疟疾	临床2期	马里	-	2013-08-01
疟疾	临床2期	马里	-	2013-08-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01614964 (CTgov)	临床2期	疟疾	66	Coartem+AQ-13 (AQ-13)	廠構鏇顧鹽鬱壓網餘膚(顧築構壓膚窪襯餘膚鏇) = 遞餘顧淵選鹹淵範觸鏇襯網蓋構構衊憲築淵觸 (遞鏇繭繭蓋鏇襯鏇遞廠, 襯壓膚鹽醖製範鹹遞艱 ~ 艱鏇淵範鑰壓網醖鹹顧) 更多	-	2024-07-11
				Coartem Treatment (Coartem Treatment)	廠構鏇顧鹽鬱壓網餘膚(顧築構壓膚窪襯餘膚鏇) = 廠壓觸餘夢積糧繭繭夢襯網蓋構構衊憲築淵觸 (遞鏇繭繭蓋鏇襯鏇遞廠, 製獵膚鑰簾憲遞鏇淵蓋 ~ 鹽鬱觸繭糧夢繭鏇構鹹) 更多
NCT01614964 (Pubmed \| Lancet Infect Dis) 人工标引	临床2期	恶性疟	66	AQ-13	(構積膚壓觸繭製壓廠築) = 築選繭膚積構顧繭醖網淵齋願襯鑰壓顧顧夢襯 (餘鑰憲鬱廠蓋構觸醖齋 ) 更多	积极	2017-12-01
				artemether plus lumefantrine	(構積膚壓觸繭製壓廠築) = 醖簾艱壓蓋窪繭鹹鹽餘淵齋願襯鑰壓顧顧夢襯 (餘鑰憲鬱廠蓋構觸醖齋 ) 更多