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

+ [17]

靶点-

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

肝细胞癌结肠转移性腺癌转移性结直肠癌+ [2]

原研机构

Fresenius Kabi AG

在研机构

Fresenius Kabi USA LLC

非在研机构

Verlyx Pharma, Inc.

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

分子式C19H24N4O2

InChIKeyXDRYMKDFEDOLFX-UHFFFAOYSA-N

CAS号100-33-4

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关联

29

项与喷他脒依西酸盐相关的临床试验

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]

NCT02210182 / Completed临床1期

A Phase I Clinical Study on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

The purpose of this study is to investigate on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

开始日期2014-08-01

申办/合作机构

Verlyx Pharma, Inc.

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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2,507

项与喷他脒依西酸盐相关的文献（医药）

2025-02-01·Current Computer-Aided Drug Design

Insights to Design New Drugs against Human African Trypanosomiasis Targeting Rhodesain using Covalent Docking, Molecular Dynamics Simulations, and MM-PBSA Calculations

Article

作者: dos Santos Nascimento, Igor José ; Santos, Mirelly Barbosa ; de Moura, Ricardo Olimpio ; De Jesus Marinho, Washley Phyama

Background:Neglected tropical diseases (NTDs) are parasitic and bacterial diseases that affect approximately 149 countries, mainly the poor population without basic sanitation. Among these, Human African Trypanosomiasis (HAT), known as sleeping sickness, shows alarming data, with treatment based on suramin and pentamidine in the initial phase and melarsoprol and eflornithine in the chronic phase. Thus, to discover new drugs, several studies point to rhodesain as a promising drug target due to the function of protein degradation and intracellular transport of proteins between the insect and host cells and is present in all cycle phases of the parasite.Methods:Here, based on the previous studies by Nascimento et al. (2021) [5], that show the main rhodesain inhibitors development in the last decade, molecular docking and dynamics were applied in these inhibitors datasets to reveal crucial information that can be into drug design.Results:Also, our findings using MD simulations and MM-PBSA calculations confirmed Gly19, Gly23, Gly65, Asp161, and Trp184, showing high binding energy (ΔGbind between -72.782 to -124.477 kJ.mol-1). In addition, Van der Waals interactions have a better contribution (-140,930 to -96,988 kJ.mol-1) than electrostatic forces (-43,270 to -6,854 kJ.mol-1), indicating Van der Waals interactions are the leading forces in forming and maintaining ligand-rhodesain complexes. Thus, conventional and covalent docking was employed and highlighted the presence of Michael acceptors in the ligands in a peptidomimetics scaffold, and interaction with Gly19, Gly23, Gly65, Asp161, and Trp184 is essential to the inhibiting activity. Furthermore, the Dynamic Cross-Correlation Maps (DCCM) show more correlated movements for all complexes than the free rhodesain and strong interactions in the regions of the aforementioned residues. Principal Component Analysis (PCA) demonstrates complex stability corroborating with RMSF and RMSD.Conclusion:This study can provide valuable insights that can guide researchers worldwide to discover a new promising drug against HAT.

2024-10-12·Journal of Biomolecular Structure and Dynamics

Thiadiazine thione derivatives as anti-leishmanial agents: synthesis, biological evaluation, structure activity relationship, ADMET, molecular docking and molecular dynamics simulation studies

Article

作者: Shah, Muhammad Ishaq Ali ; Zada, Amir ; Fu, Chaoping ; Khan, Rasool ; Lodhi, Muhammad Arif ; Ibrahim, Mohammad ; Khan, Sher Wali ; Ali, Arif ; Ateeq, Muhammad ; Tamanna ; Khan, Shafi Ullah ; Qadir, Meshil ; Htar, Thet Thet ; Shtaiwi, Amneh ; Naeem, Mohammad

During last decades, 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, ¹H-NMR, ¹³C-NMR and Mass spectrometry, and finally evaluated against Leishmania major. Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC₅₀ values in the range of (1.30- 149.98 uM). Among the evaluated compounds such as 3, 4, 6, and 10 exhibited excellent leishmanicidal activities with IC₅₀ values of (2.17 μM), (2.39 μM), (2.00 μM), and (1.39 μM), respectively even better than the standard amphotericin B (IC₅₀ = 0.50) and pentamidine (IC₅₀ = 7.52). In order to investigate binding interaction of the most active compounds, molecular docking study was conducted with Leishmania major. Further molecular dynamic simulation study was also carried out to assess the stability and correct binding of the most active compound 10, within active site of the Leishamania major. Likewise, the physiochemical properties, drug likeness, and ADMET of the most active compounds were investigated, it was found that none of the compounds violate Lipiniski's rule of five, which show that this class of compounds had enough potential to be used as drug candidate in near future.Communicated by Ramaswamy H. Sarma.

2024-10-08·The American Journal of Tropical Medicine and Hygiene

Effectiveness of Antileishmanial Treatments in Three Endemic Areas of Colombia: A Community-Based Cohort Study

Article

作者: Castillo, Ruth Mabel ; Gutiérrez, Yeison ; Castaño Grajales, Patricia ; Alexander, Neal ; Del Castillo, Alejandra María ; Cossio, Alexandra ; Castro, María del Mar

The effectiveness of treatment of cutaneous leishmaniasis (CL) in rural settings remains underexplored. This study assessed the effectiveness of standard antileishmanial treatments using a community-based approach supported by mobile health (mHealth) in three rural areas of Colombia. From January 2018 to September 2021, we assessed treatment outcomes, adherence, and adverse drug reactions in CL patients, with the support of the Guaral+ST app. Treatment decisions were made by providers at health facilities at each site in accordance with national guidelines, whereas treatment follow-up and presumptive case identification were made by trained community leaders and health agents at the community level. In total, 231 participants received antileishmanial treatment (63 received miltefosine, 110 meglumine antimoniate, and 58 pentamidine). Disease presentation was mild (median number of lesions = 1, interquartile range [IQR]: 1–2) and of short duration (1.5 months, IQR: 1–3). The strategy yielded information on the therapeutic outcomes in 81% of study participants. Effectiveness, measured as the proportion of cure at 90 to 180 days, was 86.3% (95% CI: 73.3–93.48) for miltefosine; 77.6% (67.5–85.3) for meglumine antimoniate, and 73.1% (59.0–83.6) for pentamidine. The effectiveness of pentamidine in children ≤10 years old was 79.4% (61.6–90.3). This is one of the few reports of effectiveness of pentamidine in children with prospective data collection in the Americas. Adverse drug reactions occurred in 32% of patients, most frequently with meglumine antimoniate. Our findings demonstrate that standard antileishmanial treatments are effective in rural areas where the disease is endemic and that mHealth has a pivotal role in improving patient follow-up and data collection on therapeutic outcomes.

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
肝细胞癌	临床2期	加拿大	Verlyx Pharma, Inc.	2014-08-01
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
胰腺癌	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

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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)	(憲鬱鹹顧鬱夢淵襯蓋齋) = 膚獵壓醖積齋範築範膚齋簾鹹鹽範餘鏇窪壓糧 (鏇獵餘遞窪願蓋齋醖蓋, 製壓壓鹽鬱願壓窪鏇餘 ~ 醖鏇製齋衊壓鏇構夢廠) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	(憲鬱鹹顧鬱夢淵襯蓋齋) = 淵鹽範艱遞膚醖齋願窪齋簾鹹鹽範餘鏇窪壓糧 (鏇獵餘遞窪願蓋齋醖蓋, 獵夢襯鬱淵遞襯繭鬱夢 ~ 鏇製觸窪餘襯廠顧蓋糧) 更多	-	2023-11-22
NCT03096457 (Pubmed \| Clin Infect Dis)	临床2/3期	皮肤利什曼病	80	15% Paromomycin-Aquaphilic	(艱願鏇願蓋醖壓夢襯獵) = 衊鹽膚築繭網鏇簾鹽構衊廠衊範願糧選築顧膚 (築蓋獵憲餘鹹醖築製艱, 62.5 ~ 88)	-	2019-02-15
NCT03096457 (Pubmed \| Clin Infect Dis)	临床2/3期	皮肤利什曼病	80	Aquaphilic vehicle	(艱願鏇願蓋醖壓夢襯獵) = 淵齋壓選範鬱繭獵衊糧衊廠衊範願糧選築顧膚 (築蓋獵憲餘鹹醖築製艱, 3 ~ 30)	-	2019-02-15
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	(獵願壓顧衊構積衊築構) = 淵構積鬱夢壓淵遞網繭鹽艱網築糧艱艱壓廠醖 (憲醖範選簾憲鬱夢鏇壓, 21.7) 更多	-	2013-06-01
ASCO2006	N/A	肺孢子菌肺炎二线	100	Intravenous pentamidine	糧壓艱鹽廠遞餘蓋淵壓(願簾憲築鹹鏇製範獵簾) = 鬱鏇築壓簾壓廠鏇觸襯壓築積鏇築簾鹹構艱繭 (獵鏇繭淵鹽蓋繭製糧製 )	-	2006-06-20