帕呋拉定(Pafuramidine maleate) - 药物靶点：Top II_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pafuramidine、Pafuramidine maleate (USAN)、Parfuramidine maleate

+ [2]

靶点

Top II

作用机制

Top II抑制剂(拓扑异构酶II抑制剂)

治疗领域

免疫系统疾病感染呼吸系统疾病+ [2]

在研适应症-

非在研适应症

获得性免疫缺陷综合征疟疾肺孢子菌肺炎+ [2]

原研机构

UNC Systems AB

在研机构-

非在研机构

Immtech Pharmaceuticals, Inc.北京华元龙医药科技发展有限公司

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评孤儿药 (美国)

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结构

分子式C24H24N4O7

InChIKeySWMNGXODFOCPKQ-BTJKTKAUSA-N

CAS号837369-26-3

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关联

7

项与帕呋拉定相关的临床试验

NCT00619346 / Terminated临床1期

Randomized, Double-Blind Phase 1 Safety and Tolerability Study of Pafuramidine Maleate (DB289) in Healthy Subjects

This is a phase 1 study to establish the safety and tolerability profile of pafuramidine maleate 100 mg BID administered orally for 14 days to healthy subjects

开始日期2007-11-01

申办/合作机构

Immtech Pharmaceuticals, Inc.

NCT00408369 / Completed临床1/2期

Prophylactic Antimalarial Activity of DB289 in Volunteers Challenged With Plasmodium Falciparum

To evaluate the prophylactic activity of orally administered DB289 against Plasmodium falciparum in non-immune healthy volunteers who are challenged by the bite of five P. falciparum-infected Anopheles stephensi mosquitoes

开始日期2006-11-01

申办/合作机构

Immtech Pharmaceuticals, Inc.

NCT00302341 / Terminated临床3期

International Randomized, Controlled Phase 3 Trial of DB289 Versus Trimethoprim-sulfamethoxazole for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP) in Patients With HIV/AIDS

The purpose of this study is to demonstrate the non-inferiority of pafuramidine maleate (DB289)versus trimethoprim-sulfamethoxazole (TMP-SMX)for the treatment of mild to moderately severe Pneumocystis pneumonia (PCP).

开始日期2006-05-01

申办/合作机构

Immtech Pharmaceuticals, Inc.

100 项与帕呋拉定相关的临床结果

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100 项与帕呋拉定相关的转化医学

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100 项与帕呋拉定相关的专利（医药）

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36

项与帕呋拉定相关的文献（医药）

2019-08-09·ACS Pharmacology & Translational Science

Combination Treatment of Erythromycin and Furamidine Provides Additive and Synergistic Rescue of Mis-splicing in Myotonic Dystrophy Type 1 Models

Article

作者: Yang, Hongfen ; Nakamori, Masayuki ; Berglund, J. Andrew ; Huigens III, Robert W. ; Jenquin, Jana R.

Myotonic dystrophy type 1 (DM1) is a multi-systemic disease that presents with clinical symptoms including myotonia, cardiac dysfunction and cognitive impairment. DM1 is caused by a CTG expansion in the 3' UTR of the DMPK gene. The transcribed expanded CUG repeat RNA sequester the muscleblind-like (MBNL) and up-regulate the CUG-BP Elav-like (CELF) families of RNA-binding proteins leading to global mis-regulation of RNA processing and altered gene expression. Currently, there are no disease-targeting treatments for DM1. Given the multi-step pathogenic mechanism, combination therapies targeting different aspects of the disease mechanism may be a viable therapeutic approach. Here, as proof-of-concept, we studied a combination of two previously characterized small molecules, erythromycin and furamidine, in two DM1 models. In DM1 patient-derived myotubes, rescue of mis-splicing was observed with little to no cell toxicity. In a DM1 mouse model, a combination of erythromycin and the prodrug of furamidine (pafuramidine), administered orally, displayed both additive and synergistic mis-splicing rescue. Gene expression was only modestly affected and over 40 % of the genes showing significant expression changes were rescued back toward WT expression levels. Further, the combination treatment partially rescued the myotonia phenotype in the DM1 mouse. This combination treatment showed a high degree of mis-splicing rescue coupled with low off-target gene expression changes. These results indicate that combination therapies are a promising therapeutic approach for DM1.

2017-07-01·Nature Reviews Microbiology

Erratum: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need

Article

作者: Wyllie, Susan ; Horn, David ; Gilbert, Ian H. ; Read, Kevin D. ; Field, Mark C. ; Wyatt, Paul G. ; Fairlamb, Alan H. ; Torrie, Leah S. ; Gray, David W. ; De Rycker, Manu ; Ferguson, Michael A. J.

A review.In figure 2b of this article, the structures of Pafuramidine and DB75 were incorrect.The mistakes have been corrected in the PDF and online.

2016-02-01·PLoS neglected tropical diseases

Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.

Article

作者: Mutantu, Pierre Nsele ; Dituvanga, Ndinga Dieyi ; Lubaki, Jean-Pierre Fina ; Mintwo, Alain Fukinsia ; N'tombe, Patrick Mangoni ; Macharia, Stephen ; Munungu, Blaise Fungula ; Franco, Jose Ramon ; Mpoto, Alfred Mpoo ; Deo, Gratias Kambau Manesa ; Mpanya, Alain ; Munungi, Augustin Kayeye ; Dala, Amadeu ; Burri, Christian ; Mesu, Victor Kande Betu Ku ; Olson, Carol A ; Kuikumbi, Florent Mbo ; Bernhard, Sonja C ; Pohlig, Gabriele ; Tidwell, Richard R ; Blum, Johannes ; Bilenge, Constantin Miaka Mia

BACKGROUNDSleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine.METHODSThis was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.FINDINGS/CONCLUSIONSThe overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity.

100 项与帕呋拉定相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06629	帕呋拉定	-	DB06532

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
锥虫病	临床3期	中国	北京华元龙医药科技发展有限公司	2007-08-22
锥虫病	临床3期	中国	Immtech Pharmaceuticals, Inc.	2007-08-22
疟疾	临床3期	美国	Immtech Pharmaceuticals, Inc.	2006-11-01
肺孢子菌肺炎	临床3期	美国	Immtech Pharmaceuticals, Inc.	2006-05-01
非洲锥虫病	临床3期	安哥拉	Immtech Pharmaceuticals, Inc.	2001-08-01
非洲锥虫病	临床3期	刚果共和国	Immtech Pharmaceuticals, Inc.	2001-08-01
获得性免疫缺陷综合征	临床2期	美国	Immtech Pharmaceuticals, Inc.	2006-05-01