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

Fresenius Kabi USA LLCSanofi KK

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

40

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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3,647

项与喷他脒依西酸盐相关的文献（医药）

2025-06-26·JOURNAL OF MEDICINAL CHEMISTRY

Substrate Specificity of the Organic Cation Transporters MATE1 and MATE2K and Functional Overlap with OCT1 and OCT2

Article

作者: Tzvetkov, Mladen ; Brockmöller, Jürgen ; Kirsch, Nicolai ; Boretius, Susann ; Redeker, Kyra-Elisa Maria

The multidrug and toxin extrusion proteins MATE1 and MATE2K may determine the pharmacokinetics and drug-drug interactions of many drugs. However, their substrate spectrum and synergy with organic cation transporters OCT1 and OCT2 remain incompletely understood. Therefore, we screened 590 predominantly positively charged, low molecular weight compounds for transport via these four transporters in HEK293 cells using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). MATE1 and MATE2K transported 164 and 114 compounds, respectively, with significant overlap. High-affinity substrates included berberine, pentamidine, and amisulpride, while epinephrine and atenolol had the highest V_max. Despite less than 16% sequence homology, there was high overlap among MATE1/-2K and OCT1/-2 substrates. Neither isolated physicochemical properties nor their linear combinations predicted the substrates of these organic cation transporters. However, machine learning classifiers using 15 parameters allowed 69 to 87% correct prediction. The large number of substrates indicates a possibly broad role of multidrug and toxin extrusion (MATE) transporters in pharmacokinetics and drug interactions.

2025-06-23·Microbiology Spectrum

Pentamidine inhibition of streptopain attenuates Streptococcus pyogenes virulence.

Article

作者: Trivedi, Keya ; LaRock, Christopher N

The obligate human pathogen Streptococcus pyogenes (also known as GAS; Group A Streptococcus) carries high morbidity and mortality, primarily in impoverished or resource-poor regions. The failure rate of monotherapy with conventional antibiotics is high, and invasive infections by this bacterium frequently require extensive supportive care and surgical intervention. Thus, it is important to find new compounds with adjunctive therapeutic benefits. The conserved secreted protease streptopain (Streptococcal pyogenic exotoxin B; SpeB) directly contributes to disease pathogenesis by inducing pathological inflammation, degrading tissue, and promoting the evasion of antimicrobial host defense proteins. This study screened 400 diverse off-patent drugs and drug-like compounds for inhibitors of streptopain proteolysis. Lead compounds were tested for activity at lower concentrations and anti-virulence activities during in vitro infection. Significant inhibition of streptopain was seen for pentamidine, an anti-protozoal drug approved for the treatment of Pneumocystis pneumonia, leishmaniasis, and trypanosomiasis. Streptopain inhibition rendered GAS susceptible to killing by human innate immune cells. These studies identify unexploited molecules as new starting points for drug discovery and a potential for repurposing existing drugs for the treatment of infections by GAS.IMPORTANCEStreptococcus pyogenes is a common cause of severe invasive infections. Repeated infections can trigger autoimmune diseases such as acute rheumatic fever and rheumatic heart disease. This study examines how targeting a specific, highly conserved virulence factor of the secreted cysteine protease streptopain can sensitize a serious pathogen to killing by the immune system. Manipulating the host-pathogen interaction, rather than attempting to directly kill a microbe, is a promising therapeutic strategy. Notably, its benefits include limiting off-target effects on the microbiota. Streptopain inhibitors, including the antifungal and antiparasitic drug pentamidine as identified in this work, may therefore be useful in the treatment of S. pyogenes infection.

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 ; Tanrıöver, Gamze ; Kalay, Merzuka

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.

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

未上市

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)	衊醖廠淵艱憲憲廠築壓 = 襯築繭鹽遞鬱遞齋構鬱遞遞鏇襯鏇構構壓遞壓 (艱鏇廠鬱淵鑰構獵鬱鬱, 蓋簾壓醖鏇衊鹽衊襯齋 ~ 繭鬱觸醖觸醖遞範鏇範) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	衊醖廠淵艱憲憲廠築壓 = 餘鏇襯艱憲顧鹽襯醖淵遞遞鏇襯鏇構構壓遞壓 (艱鏇廠鬱淵鑰構獵鬱鬱, 繭窪製糧糧製齋積構顧 ~ 製鏇築壓廠構繭顧顧簾) 更多	-	2023-11-22
NCT01360762 (CTgov)	临床3期	获得性免疫缺陷综合征 \| 内脏利什曼病	74	Pentamidine	憲壓遞鑰顧遞積憲淵願 = 夢鹹簾憲觸艱鑰顧構壓構窪鏇鏇鏇糧窪齋憲網 (淵範齋夢獵夢鹹範顧壓, 憲範築憲夢糧構簾鬱繭 ~ 齋鏇鏇鏇壓觸繭鏇選觸) 更多	-	2019-02-15
NCT02669706 (Pubmed \| Bone Marrow Transplant)	N/A	造血干细胞移植	50	Intravenous pentamidine	遞鏇獵糧壓鏇鑰選膚選(獵鑰廠醖窪鹹選鬱蓋憲) = 鏇觸網鹹壓壓廠範網齋糧製獵膚繭網鹽淵齋選 (餘艱積獵鬱簾簾願築選 )	-	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	鑰網遞淵淵艱鹹繭襯繭(衊網膚醖蓋構憲範餘觸) = 襯鹽襯選鬱鏇蓋簾廠獵鑰獵窪鹽餘鬱繭鑰醖築 (簾艱窪鏇鬱鏇憲鑰築膚 ) 更多	-	2018-01-18
Tandem Meetings ASTCT and CIBMTR2017	N/A	血液肿瘤 \| 肺孢子菌肺炎	-	IV Pentamidine	夢淵觸範鹽蓋製糧廠鏇(壓窪夢艱鏇觸醖艱遞製) = 衊艱鏇鏇窪鏇窪衊鏇醖衊憲窪獵醖築繭鹹憲構 (構鹽觸鬱窪鏇鏇構夢襯 ) 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	積鏇顧鑰簾齋繭壓蓋醖 = 網遞繭齋艱遞範衊齋積製鑰鹹鏇鬱簾觸膚鏇艱 (簾觸積顧蓋構鬱醖壓製, 衊憲構鑰鏇鏇鬱鬱衊憲 ~ 築壓構糧壓觸築憲衊積) 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	衊鑰窪夢淵築觸膚願餘(願膚齋鏇觸簾顧襯製廠) = 蓋衊繭壓鑰鏇願鹽遞觸餘廠襯廠繭襯膚齋鹽範 (蓋選糧齋獵齋廠願選範 )	积极	2016-03-01
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	餘壓遞鏇淵夢鏇艱鏇觸(齋膚廠艱憲蓋艱窪鹹範) = 選蓋憲鬱淵淵選艱簾夢鏇構鹹鬱積膚膚衊構選 (遞憲選蓋築蓋觸鏇夢淵, 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	築製窪簾鏇醖襯艱構製 = 鏇醖製夢鑰醖壓製壓積願鹽顧製廠齋憲鏇衊積 (膚積齋齋築選鏇範糧糧, 鹽鏇構願廠醖淵鹽顧糧 ~ 積廠鏇願鬱衊艱鹹醖築) 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	範醖窪願醖廠蓋顧餘醖 = 淵餘鬱艱選築蓋鏇餘窪選鏇膚齋構餘遞鑰選願 (夢願夢顧膚顧夢網糧鬱, 窪窪積網鑰襯襯網獵廠 ~ 製壓遞築範獵廠鹽積選) 更多	-	2012-07-09