喷他脒依西酸盐(Pentamidine Isethionate) - 在研适应症：肺孢子菌肺炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

1,5-bis(4-amidinophenoxy)pentane、4,4'-(1,5-pentanediylbis(oxy))bis-benzenecarboximidamide、4,4'-(pentamethylenedioxy)dibenzamidine

+ [19]

靶点-

作用方式-

作用机制-

治疗领域

感染呼吸系统疾病其他疾病

在研适应症

肺孢子菌肺炎

非在研适应症

晚期胰腺腺癌肝细胞癌结肠转移性腺癌+ [2]

原研机构

Fresenius Kabi AG

在研机构

Sanofi KK

Fresenius Kabi USA LLC

非在研机构

Verlyx Pharma, Inc.

权益机构-

最高研发阶段批准上市

首次获批日期

美国 (1984-10-16),

肺孢子菌肺炎

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C23H36N4O10S2

InChIKeyYBVNFKZSMZGRAD-UHFFFAOYSA-N

CAS号140-64-7

关联

39

项与喷他脒依西酸盐相关的临床试验

NCT03730363

/ Completed临床1期IIT

A Phase I Study of Pentamidine in Combination With Salvage Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma

Primary Objective:
To evaluate dose limiting toxicity and to determine the recommended phase 2 dose (RP2D) of pentamidine in combination with salvage chemotherapy with ifosfamide, carboplatin and etoposide (ICE) on a 3-weeks schedule in relapsed/refractory classical Hodgkin lymphoma (cHL).
Secondary Objective:
To estimate the overall best treatment response at 5- and 16-weeks from study enrollment. Although the clinical benefit of these drugs in combination has not been established, offering this treatment may provide a therapeutic benefit. The patients will be carefully monitored for tumor response and symptom relief, in addition to safety and tolerability.
To estimate the duration of response to the proposed combined therapy.
To measure the protein of regenerating liver-3 (PRL-3) level of expression in patients at time of relapse.
To measure circulating biomarkers of response (soluble CD30 (sCD30), and thymus and activation-related chemokine (TARC)) in serum samples collected throughout treatment and inhibition of (pSTAT, pAKT) in peripheral blood mononucleated cells (PBMC).
Exploratory Objective:
To measure cell-free messenger RNA (cfmRNA) in peripheral blood.
To measure cell-free DNA in peripheral blood

开始日期2018-12-19

申办/合作机构

University of Kentucky

NCT03403621

/ Terminated临床1/2期IIT

Double Blind, Single-Center, Randomized, Within Subject Placebo, Phase I Study Evaluating the Effects of Novel Topical Gel in Prevention of Hypertrophic Scar Formation

Researchers are trying to find out more about the side effects of topical (applied to the skin) Pentamidine, to determine if it is safe for use in people. They also want to find out if topical use of Pentamidine can help treat hypertrophic scars.
Pentamidine is a medicine that is currently used to treat certain kinds of infection. It is most often given by intravenous (into a vein) or inhalation (through a breathing device). This medication is approved by the U.S. Food and Drug Administration (FDA) for use in these forms.
Everyone in this study will receive topical Pentamidine (TP) in a silicone based gel (PCCA Pracasil Plus). Topical treatment of Pentamidine is still experimental and has not been formally tested for safety or effectiveness in a randomized control trial within the United States. The FDA has allowed the use of topical Pentamidine in this research study.

开始日期2018-03-05

申办/合作机构

Mayo Clinic

NCT03201159

/ Withdrawn临床1期IIT

A Pilot, Exploratory Dose Escalating Study on the Safety, Pharmacodynamics and Preliminary Efficacy of VLX103 in the Treatment of Moderate Alcoholic Steatohepatitis

The study drug (VLX103) is being developed for the treatment of Alcoholic Steatohepatitis and other liver diseases. Alcoholic Steatohepatitis is an inflammatory (associated with irritation, swelling and cell damage) disease that affects the liver. It is associated with heavy and chronic intake of alcohol and presence of fat in the liver. Signs and symptoms often include fever, yellowing of the skin, nausea and impairment of liver function.
The main objective of this study is to evaluate the safety, pharmacodynamics (what the drug does to the body) and pharmacokinetics (how the drug is handled by the human body, like absorption and elimination) of increasing doses of VLX103 in subjects with moderate Alcoholic Steatohepatitis. In other words, we will evaluate how your body tolerates VLX103 at a specific dose and the effects that this VLX103 dose has on your liver and your body in general. The secondary objectives of this study are to evaluate if VLX103 has the potential to treat Alcoholic Steatohepatitis patients, to determine the maximum dose that can be tolerated, and to measure the levels of VLX103 in your blood at different time points during the study.
VLX103 is an experimental drug. Experimental means that the drug has not been approved by the Food and Drug Administration (FDA) for the treatment of Alcoholic Steatohepatitis. The active ingredient in VLX103, pentamidine, is approved for treating parasitic (microorganisms) infections. Pentamidine is currently approved and marketed in about 20 countries, including the United States, for use by injection (administered by a syringe) and by inhalation (administered by a nebulizer) for other health conditions. However, VLX103 is the first oral form of pentamidine being developed, and is administered by mouth as an oral tablet.

开始日期2017-06-25

申办/合作机构

National Institute on Alcohol Abuse & Alcoholism

[+3]

100 项与喷他脒依西酸盐相关的临床结果

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100 项与喷他脒依西酸盐相关的转化医学

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100 项与喷他脒依西酸盐相关的专利（医药）

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3,620

项与喷他脒依西酸盐相关的文献（医药）

2025-06-01·NEUROPHARMACOLOGY

Vortioxetine attenuates rotenone-induced enteric neuroinflammation via modulation of the TLR2/S100B/RAGE signaling pathway in a rat model of Parkinson's disease

Article

作者: Özbey, Gül ; Yıldırım, Sendegül ; Maytalman, Erkan ; Samur, Dilara Nemutlu ; Kalay, Merzuka ; Tanrıöver, Gamze

Emerging evidence suggests that gastrointestinal dysfunction and enteric nervous system pathology play a critical role in the early stages of Parkinson's disease. Considering the bidirectional relationship between gastrointestinal symptoms and mood disorders, this study aimed to elucidate the effects and possible mechanisms of action of vortioxetine, a serotonergic antidepressant, on the pathophysiological changes induced by rotenone in the enteroglial cells. α-synuclein, phosphorylated α-synuclein, TLR2, S100B and RAGE expression were detected in duodenal tissues of rats administered rotenone (2 mg/kg/day, s.c.) and/or vortioxetine (10 mg/kg/day, s.c.) for 28 days. For the mechanism of action studies, rat-derived enteroglial cells were treated with rotenone (10 μM) and/or vortioxetine (5 μM or 1 μM) for 24 h. The effects of vortioxetine were evaluated in the presence of the TLR2 antagonist C29, RAGE antagonist FPS-ZM1 and the S100B inhibitor pentamidine. TLR2, S100B, RAGE, and NFκB mRNA levels and proinflammatory cytokines via RT-qPCR and ELISA. Our results demonstrate that rotenone treatment significantly increased α-synuclein, pS129-α-synuclein, TLR2, and S100B expression while reducing RAGE levels, indicating marked enteric pathology. Vortioxetine administration attenuated these effects, reducing α-synuclein accumulation and proinflammatory markers. In vitro, rotenone impaired glial responses, decreasing S100B, RAGE, and NFκB markers, while vortioxetine improved these responses, promoting resynthesis of inflammatory molecules. Notably, S100B, NFκB, and cytokine levels (TNF-α, IL-1β, IL-6) were affected by C29, FPS-ZM1, and pentamidine pretreatments. Thus, vortioxetine is thought to have beneficial effects on rotenone-induced pathological changes in EGCs, and some of these effects are thought to be mediated by the TLR2/S100B/RAGE pathway.

2025-06-01·MYCOPATHOLOGIA

Synergistic Antifungal Activity of Pentamidine and Auranofin Against Multidrug-Resistant Candida auris

Article

作者: Lucini, Fabíola ; Retore, Yasmim Isabel ; Simionatto, Simone ; Rossato, Luana

BACKGROUND:

Candida auris is a significant clinical concern due to its ability to cause outbreaks in healthcare settings and its common resistance to current treatments. This highlights the need for alternative therapies. Drug repurposing offers a promising approach, and the combination of pentamidine (antiprotozoal) and auranofin (anti-rheumatic) has shown potential antifungal activity against Candida species, including C. auris. This study aimed to evaluate the antifungal activity of pentamidine and auranofin, both individually and in combination, against C. auris.

METHODS:

Minimum Inhibitory Concentrations (MICs) were determined following CLSI guidelines, and drug interactions were assessed using the checkerboard microdilution method. Additional evaluations included growth inhibition, antibiofilm activity, cell damage, sorbitol protection, and efflux pump inhibition. Nucleotide leakage and cell membrane permeability were analyzed using biochemical assays. In vivo efficacy was tested using a Tenebrio molitor larvae model infected with C. auris.

RESULTS:

The MICs of pentamidine against C. auris ranged from 16 to 128 μg/mL, showing fungicidal activity. The combination with auranofin had a synergistic effect (FICI: 0.37) and exhibited a fungistatic effect in growth inhibition assays. Auranofin was most effective at inhibiting biofilm formation. Pentamidine impaired mitochondrial function, leading to cellular respiration issues and membrane damage. Efflux pump assays indicated activation by both drugs, potentially influencing resistance. In vivo tests showed both drugs significantly improved survival rates in infected larvae compared to fluconazole.

CONCLUSION:

In conclusion, pentamidine and auranofin, either individually or in combination, are promising treatments for C. auris and warrant further research into optimal dosing and combination strategies.

2025-05-14·mBio

Discovery of novel antifungal drugs via screening repurposing libraries against Coccidioides posadasii spherule initials

Article

作者: Liao, Yu-Rou ; Saeger, Sarah ; Hung, Chiung-Yu ; Campuzano, Althea ; Lopez-Ribot, Jose ; Yu, Jieh-Juen ; West-Jeppson, Kathryn

ABSTRACT:

Coccidioidomycosis or valley fever is a treatment-limited fungal infection endemic to the alkaline deserts of North and South America for which two classes of antifungals are typically used: the polyenes and the triazoles. In light of the limited usefulness of the echinocandins and a growing trend of azole resistance, it is essential that we identify novel antifungals. In this study, we have developed and optimized a screening methodology for identifying potential antifungals effective against Coccidioides spherule initials using a metabolic assay, used it to screen four diverse drug libraries with limited drug overlap, and established safety and efficacy data for a majority of the compounds, including the Broad Repurposing Hub, Prestwick Chemicals 1520, Selleck L8200 Anti-parasitic, and MedChemExpress CNS Penetrants libraries. Hits were defined as compounds with strong metabolic inhibition (≥70%), which were significantly different compared to the median plate readout (B-scores ≤ −3). We identified 30 promising hits and found 12 compounds exhibiting half-maximal inhibitory concentrations below 6 µM. Among these, oxethazaine, niclosamide ethanolamine, 10058-F4, niclosamide (NIC), and pentamidine isethionate showed synergy with amphotericin B, suggesting their potential use in combination therapy. Further assessment of lead compounds’ effects on spherules was conducted by image flow cytometry. Additionally, we explored the potential to use an attenuated, Biosafety Level 2 containment mutant, C. posadasii ∆ cts2 /∆ ard1 /∆ cts3 (∆T), as a surrogate model for drug screening. Overall, our findings provide a foundation for future research focused on screening and developing novel coccidioidomycosis treatments.

IMPORTANCE:

The antifungal treatment arsenal is especially limited against Coccidioides . Due to toxicity concerns, amphotericin B is generally reserved for triazole-recalcitrant infections. Recent laboratory susceptibility tests show an increase in fluconazole resistance, highlighting a need for new treatments. We have developed a large-scale metabolic screening assay under Biosafety Level 3 containment to identify existing drugs with novel activity against Coccidioides spherules. This drug-repurposing approach represents a convenient and cost-effective strategy to increase the available antifungals effective against these infections.

1

项与喷他脒依西酸盐相关的新闻（医药）

2024-03-07

·Business Wire

Montdorex Announces Acceptance of Its Abstract for Presentation at the AACR Annual Meeting 2024

MONTREAL--( BUSINESS WIRE )--Montdorex Inc. (“Montdorex” or “the Company”), a privately-owned precision medicine company, today announced that Terry Chow, Ph.D., Founder and CEO will present insights on the relevance of inhibiting the endo-exonuclease (EE) enzyme in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting, to be held in San Diego, CA, April 5-10, 2024. The endo-exonuclease enzyme plays a key role in DNA damage repair mechanisms, but it is also overexpressed in cancer tumors. In a proof-of-concept study, Montdorex showed that tumors with increased EE expression showed the best response to pentamidine, an endo-exonuclease inhibitor. The Company has also identified mono- and di-amidine analogs of pentamidine that are more effective than the parent drug in both in vitro and in vivo studies. “Our lead candidate, MTDX203, showed an increased anti-cancer activity with a higher safety index than pentamidine in preclinical animal studies,” said Terry Chow of Montdorex. “I look forward to presenting our detailed findings to the AACR scientific and investor community at the upcoming annual meeting.” Details of the AACR poster presentation are as follows: Poster Presentation (#5604): Modulating DNA repair through endo-exonuclease inhibition: a new therapeutic paradigm in Oncology [ link to the abstract ] Session Category: Molecular/Cellular Biology and Genetics Session Title: DNA Damage and Repair 2 Session Date and Time: Tuesday, April 9, 2024 1:30 PM – 5:00 PM (PT) Location: Poster Section 14, Poster Board Number 2 About Montdorex Based in Montreal, Canada, Montdorex Inc. is a privately-owned, early-stage precision medicine company, targeting the endo-exonuclease (EE) enzyme involved in cancer tumor growth and inflammatory processes. The company is developing proprietary mono-amidine and di-amidine EE inhibitors to modulate DNA repair in oncology and non cytotoxic di-amidine analogs for anti-inflammatory applications, such as gastrointestinal conditions and liver diseases. For more information, please visit montdorex.com .

AACR会议临床结果

100 项与喷他脒依西酸盐相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00834	喷他脒依西酸盐	P01CX01	DB00738

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肺孢子菌肺炎	美国	Fresenius Kabi USA LLC	1984-10-16

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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
转移性非小细胞肺癌	临床2期	波兰	Verlyx Pharma, Inc.	2012-09-01
转移性结直肠癌	临床2期	加拿大	Verlyx Pharma, Inc.	2011-03-01
晚期胰腺腺癌	临床2期	加拿大	Verlyx Pharma, Inc.	2009-01-01
结肠转移性腺癌	临床2期	加拿大	Verlyx Pharma, Inc.	2008-03-01
肝细胞癌	临床1期	加拿大	Verlyx Pharma, Inc.	2014-08-01

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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


NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Pentamidine Isethionate (Topical Pentamidine Isethionate)	簾醖繭齋糧壓艱齋製構 = 繭齋觸蓋襯膚簾積願餘鏇獵蓋積襯憲鬱醖廠築 (築齋願鹽簾鹹鏇簾製選, 膚鹹顧壓糧廠糧築餘鹹 ~ 繭範選鹹膚願糧構襯夢) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	簾醖繭齋糧壓艱齋製構 = 壓膚壓廠積艱醖範鹽製鏇獵蓋積襯憲鬱醖廠築 (築齋願鹽簾鹹鏇簾製選, 鏇鏇艱獵餘餘鑰獵憲鹹 ~ 範範淵蓋選艱餘壓觸齋) 更多	-	2023-11-22
NCT01360762 (CTgov)	临床3期	获得性免疫缺陷综合征 \| 合并感染 \| 内脏利什曼病	74	Pentamidine	製選繭襯觸醖願遞獵齋 = 觸襯壓簾鏇鬱壓壓鹽範獵憲壓鹽餘積膚鬱淵築 (遞衊積衊餘製齋鹹繭餘, 膚觸廠廠鏇艱鬱膚積願 ~ 觸憲衊餘廠繭遞構淵遞) 更多	-	2019-02-15
NCT02669706 (Pubmed \| Bone Marrow Transplant)	N/A	造血干细胞移植	50	Intravenous pentamidine	顧衊膚憲構範膚積淵鑰(糧鑰齋壓蓋艱鏇廠餘鏇) = 網膚蓋築鬱繭構鬱遞遞襯繭膚廠鏇網蓋遞廠蓋 (鹽膚餘範積餘簾繭願蓋 )	-	2018-03-01
NCT01360762 (Pubmed \| Clin Infect Dis)	临床3期	HIV感染 \| 内脏利什曼病	74	Pentamidine secondary prophylaxis	壓衊觸餘夢壓鑰積夢齋(鹽糧鬱構糧簾餘糧糧鹹) = 構願齋蓋齋憲繭顧製鏇鑰顧壓壓遞鬱鏇餘廠範 (築遞獵獵蓋繭鏇鹹製衊 ) 更多	-	2018-01-18
Tandem Meetings ASTCT and CIBMTR2017	N/A	血液肿瘤 \| 肺孢子菌肺炎	-	IV Pentamidine	願膚鬱遞淵窪蓋構鑰糧(繭衊願鹹鬱顧鹽蓋鹽鬱) = 壓繭範憲簾築廠顧選糧選廠觸鏇觸遞淵遞簾鏇 (範淵製膚醖憲積範夢餘 ) 更多	-	2017-03-01
NCT00729807 (CTgov)	临床2期	难治性黑色素瘤 \| 皮肤黑色素瘤	6	pentamidine	獵餘壓窪選願淵衊網鬱 = 獵窪製積壓衊繭廠鏇製鬱簾廠築願觸鬱鹹憲鏇 (糧淵網獵鑰襯窪憲膚艱, 糧窪餘壓願繭獵製膚壓 ~ 築襯淵蓋鬱壓衊憲繭鏇) 更多	-	2016-10-21
Tandem Meetings ASTCT and CIBMTR2016	N/A	肺孢子菌肺炎 \| 造血干细胞移植	58	Intravenous Pentamidine	醖壓範齋製憲壓鏇繭衊(鹹鬱壓繭繭醖繭簾衊簾) = 獵顧廠網廠鏇齋製夢繭簾夢鹽廠願齋艱衊窪鏇 (鬱獵襯襯繭顧衊構餘艱 )	积极	2016-03-01
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	鑰積網廠範窪構範糧艱(襯鹽顧範醖鬱願齋選鹹) = 餘遞糧憲衊蓋簾選製鏇窪糧選餘顧壓醖齋糧繭 (窪鬱鏇壓鹽築鬱繭製襯, 21.7) 更多	-	2013-06-01
NCT00014911 (CTgov)	临床2期	1型糖尿病	36	Islet Transplantation+Ganciclovir+Sulfamethoxazole+Tacrolimus+Sirolimus+Daclizumab+Pentamidine+Trimethoprim	窪壓鹹遞醖製製築鹹襯 = 獵膚築構範繭獵壓鏇構衊獵鹹範範鹽淵壓廠壓 (鏇齋繭構醖獵窪醖獵壓, 鬱網製積艱齋獵鬱憲壓 ~ 積艱糧醖淵鬱壓選鹹築) 更多	-	2012-10-17
NCT00078559 (CTgov)	临床1/2期	肾脏疾病 \| 肾移植排斥反应	10	Kidney transplant+Acyclovir+Acetaminophen+Bactrim+Nystatin+Sirolimus+Clotrimazole+Trimethoprim+Diphenhydramine+TMP+Alemtuzumab+Valgancyclovir+Sulfa+Methylprednisolone+Tacrolimus+Pentamidine	鬱鹹膚顧選壓鬱膚艱遞 = 網鏇襯淵範憲選遞鹹糧獵醖選醖糧艱膚糧選觸 (鬱鏇壓鹹齋醖艱範鹽鑰, 夢衊鹽獵廠觸遞醖顧壓 ~ 選觸遞壓範壓餘鬱顧廠) 更多	-	2012-07-09