Delving into the Latest Updates on Fimbrion Therapeutics, Inc. with Synapse

概览

疾病领域	数量

感染	3

排名前五的药物类型	数量

小分子化药	2
化学药	1

排名前五的靶点	数量

QcrB	1
fimH蛋白	1
UQCRB	1

关联

5

项与 Fimbrion Therapeutics, Inc. 相关的药物

Tuberculosis(Fimbrion)

靶点

UQCRB

作用机制

UQCRB inhibitors

在研机构

Fimbrion Therapeutics, Inc.

原研机构

Fimbrion Therapeutics, Inc.

在研适应症

肺结核

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

GSK-3859747A

靶点

fimH蛋白

作用机制

fimH蛋白抑制剂

在研机构

GSK Plc [+1]

原研机构

GSK Plc

在研适应症

泌尿道感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

US20240279236

专利挖掘

靶点

QcrB

作用机制-

在研机构

St. Louis University [+2]

原研机构

Washington University in St. Louis [+2]

在研适应症

结核

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

100 项与 Fimbrion Therapeutics, Inc. 相关的临床结果

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0 项与 Fimbrion Therapeutics, Inc. 相关的专利（医药）

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5

项与 Fimbrion Therapeutics, Inc. 相关的文献（医药）

2017-07-03·Expert Opinion on Drug Discovery3区 · 医学

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

3区 · 医学

Review

作者: Mydock-McGrane, Laurel K. ; Janetka, James W. ; Hannan, Thomas J.

INTRODUCTIONThe bacterial adhesin FimH is a virulence factor and an attractive therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD). Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an integral role in the pathogenesis of UPEC. Recent efforts have culminated in the development of small-molecule mannoside FimH antagonists that target the mannose-binding lectin domain of FimH, inhibiting its function and preventing UPEC from binding mannosylated host cells in the bladder, thereby circumventing infection. Areas covered: The authors describe the structure-guided design of mannoside ligands, and review the structural biology of the FimH lectin domain. Additionally, they discuss the lead optimization of mannosides for therapeutic application in UTI and CD, and describe various assays used to measure mannoside potency in vitro and mouse models used to determine efficacy in vivo. Expert opinion: To date, mannoside optimization has led to a diverse set of small-molecule FimH antagonists with oral bioavailability. With clinical trials already initiated in CD and on the horizon for UTI, it is the authors, opinion that mannosides will be a 'first-in-class' treatment strategy for UTI and CD, and will pave the way for treatment of other Gram-negative bacterial infections.

2016-02-01·Expert Opinion on Therapeutic Patents2区 · 医学

Mannose-derived FimH antagonists: a promising anti-virulence therapeutic strategy for urinary tract infections and Crohn’s disease

2区 · 医学

Review

作者: Mydock-McGrane, Laurel K ; Cusumano, Zachary T ; Janetka, James W

INTRODUCTIONType 1 pili are utilized by Gram-negative bacteria to adhere to host tissue and thus are a key virulence factor in urinary tract infections (UTIs) and Crohn's disease (CD). This adhesion is mediated through specific binding of the terminal adhesin, FimH, to mannosylated host glycoproteins. FimH is essential for UTI pathogenesis and thus is a promising therapeutic target.AREAS COVEREDHerein, we review the structural frameworks of FimH antagonists disclosed in the patent literature. X-ray crystallographic binding studies of D-mannose and early FimH antagonists have uncovered key molecular interactions. Exploiting this knowledge, mannosides with extraordinarily high binding affinities have been designed. Structure-activity relationships (SAR) and structure-property relationship (SPR) studies have resulted in the rapid development of orally bioavailable FimH antagonists with promising therapeutic potential for UTI and CD.EXPERT OPINIONIt is our opinion that biaryl or 'two-ring' mannosides, which represent the largest and most thoroughly tested class of FimH antagonists, also hold the most promise as a novel treatment for UTIs. These antagonists have also been shown to have efficacy in treating CD. Judging from the strong preclinical data, we predict that one or more FimH antagonists will be entering the clinic within the next 1-2 years.

C-mannoside FimH antagonists as oral therapeutics for urinary tract infections

作者: McGrane, Laurel

Urinary tract infections (UTI) are one of the most common bacterial infections worldwide, with an estimated 15 million cases annually in the US alone.Uropathogenic Escherichia coli (UPEC) are the main causative agent of UTI and are responsible for >85% of all cases.Due to a high incidence of recurrence, UTI are becoming increasingly resistant to front-line antibiotics, necessitating the need for new strategies to combat these, and other, Gram-neg. bacterial infections.The virulence factor FimH is a lectin positioned at the tip of type 1 pili on UPEC that specifically binds highly mannosylated glycoproteins coating the bladder uroepithelium.FimH's mannose binding function mediates host-cell attachment and invasion, as well as the formation of intracellular biofilm colonies (IBCs), and thus, is critical for the establishment and maintenance of UTI.We have developed glycomimetic mannoside, small-mol., FimH antagonists that disrupt UPEC binding and colonization of the bladder as a novel therapy for preventing and treating UTI.Since this so-called "antivirulence" approach disarms rather than kills the bacteria, it circumvents the selective pressure which can lead to drug resistance.Through rational drug design and focused library synthesis, we have discovered several series of small-mol. biaryl O- and C-linked mannoside-based inhibitors of FimH, having up to 1 million-fold more potency than α-D-mannose in blocking UPEC binding and IBC formation.Lead C-mannosides have excellent PK properties, including long half-life and good oral bioavailability, as well as a safety profile amenable to once per day oral dosing.In mouse models of UTI, lead compounds showed robust efficacy at reducing bacterial burdens when dosed as low as 0.5 mg/kg.These efforts have led to the identification and selection of clin. candidate, GSK3882347, currently being evaluated in Phase 1b clin. trials as a novel, antibiotic-sparing treatment for acute UTI.

100 项与 Fimbrion Therapeutics, Inc. 相关的药物交易

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100 项与 Fimbrion Therapeutics, Inc. 相关的转化医学

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管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

药物发现

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2

临床前

其他

2

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当前项目

药物(靶点)	适应症	全球最高研发状态

GSK-3859747A ( fimH蛋白 )	泌尿道感染更多	临床前
Tuberculosis(Fimbrion) ( UQCRB )	肺结核更多	临床前
US20240279236 ( QcrB )	结核更多	药物发现
FIM-5240 ( Cell adhesion molecules )	泌尿道感染更多	终止
FIM-4269 ( Cell adhesion molecules )	泌尿道感染更多	终止