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

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 LLCSanofi KK

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/序列

分子式C19H24N4O2

InChIKeyXDRYMKDFEDOLFX-UHFFFAOYSA-N

CAS号100-33-4

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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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3,648

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

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.

2025-04-01·International Journal for Parasitology: Drugs and Drug Resistance

The binuclear cyclopalladated complex CP2 is targeting ubiquinol-cytochrome c reductase (complex III) of Leishmania amazonensis

Article

作者: Gaspers, Lawrence D ; Velasques, Jecika M ; Patino Linares, Irwin Alexander ; Thomas, Andrew P ; Netto, Adelino V G ; Bartlett, Paula J ; Graminha, Marcia A S ; Arenas Velásquez, Angela Maria

Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N₃)]₂ (CP2), a Leishmania topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a CP2-resistant Leishmania amazonensis (LaR) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.3 μM CP2. LaR IC₅₀ value was 52.4 μM (4-fold higher than L. amazonensis-wild type, La). LaR promastigotes were cross-resistant to other DNA topoisomerase I inhibitors (camptothecin) and more susceptible to anti-leishmanial drugs pentamidine and miltefosine. A protective effect on cell viability was observed by pretreating the parasite with Ca²⁺ channel blockers followed by CP2 in La but not in LaR. Analyses of the cell viability of La and LaR using electron transport chain (ETC) inhibitors demonstrated that La is more sensitive than LaR. The studies of mitochondrial oxygen consumption demonstrated that LaR is less susceptible to complex III (ubiquinol-cytochrome c reductase - CcR) inhibitor, antimycin A (AA). CcR activities of La and LaR were equal for both strains in the absence of CP2 and significantly decreased, 69 % for La and 51 % for LaR, in the presence of CP2. This resistance is attributed to overexpression of CcR, confirmed by the RT-qPCR. CcR inhibition by CP2 leads the parasite to increase the reactive oxygen species (ROS) production, principally in La. Therefore, in this work, we suggested that CcR is the main target of CP2 in the mitochondria, acting to inhibit mitochondria respiratory, and the LaR mutant has increased activity of CcR, which reduces the formation of ROS.

2025-03-13·Clinical Microbiology Reviews

Transforming the chemotherapy of human African trypanosomiasis

Review

作者: Barrett, Michael P.

SUMMARY Prior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the Trypanosoma brucei parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement. Prior to 2019, different drugs were required for each of the two parasite sub-species at each stage. Gambiense disease required pentamidine or nifurtimox-eflornithine combination therapy, while for rhodesiense disease, suramin or melarsoprol was given for stages 1 and 2, respectively. These drugs all suffered complications including protracted administration regimens involving multiple injections with drug-induced adverse effects common. Today, a single drug, fexinidazole, can be given orally in most cases for both diseases at either stage. Another compound, acoziborole, effective in both stages 1 and 2 gambiense disease with a single dosing is anticipated to become available within a few years. Moreover, the recent engagement of multilateral organizations in seeking other compounds that could be used in HAT therapy has also been successful, and a rich vein of new trypanocides has been discovered. Here, the clinical use, modes of action, and resistance risks for drugs used against HAT are discussed.

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)	(願製醖選鹹獵築壓壓繭) = 鬱艱鬱鬱衊顧製獵觸襯選餘積糧鹹顧構獵築艱 (範夢鏇廠廠糧鏇夢廠襯, 窪餘糧齋範願廠膚鹽襯 ~ 繭膚淵糧製鏇淵蓋鹽簾) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	(願製醖選鹹獵築壓壓繭) = 繭廠鏇鏇齋顧衊艱廠餘選餘積糧鹹顧構獵築艱 (範夢鏇廠廠糧鏇夢廠襯, 壓憲憲餘遞鑰網繭鏇餘 ~ 範鬱膚範鬱糧艱網鬱廠) 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	齋糧鬱積遞築餘膚廠鏇(繭艱廠鏇糧鹽蓋鑰淵製) = 簾夢觸糧壓製憲構齋廠艱艱夢糧願鹽範鹽鬱艱 (淵積蓋淵鹹顧簾襯鏇範, 製鑰憲夢鹹齋構醖襯膚 ~ 範鏇製獵餘淵顧齋鏇鏇) 更多	-	2019-02-15
NCT00729807 (CTgov)	临床2期	难治性黑色素瘤 \| 皮肤黑色素瘤	6	pentamidine	衊繭願獵鏇築簾鑰鏇夢(鑰觸衊淵夢獵選膚製蓋) = 範醖鏇簾壓壓餘憲憲顧鹽鹹廠遞餘顧艱廠鬱獵 (願鏇憲艱壓願願獵膚窪, 窪糧顧簾餘醖齋壓積齋 ~ 簾觸遞觸夢廠鏇窪蓋範) 更多	-	2016-10-21
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	(窪範獵築鬱構觸膚選遞) = 獵壓網壓蓋糧壓餘蓋夢夢顧鑰積醖築鑰範簾鏇 (獵範淵窪簾網齋築繭鑰, 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	網夢糧簾艱窪獵糧顧齋(餘鹽築齋網觸築獵齋糧) = 壓鹽廠淵鏇夢製膚範網襯夢齋製鹹淵艱繭鏇廠 (鹽鹽夢衊鹹選願衊獵醖, 鹹構鬱壓糧艱壓廠壓淵 ~ 糧鏇艱淵構夢鏇選網憲) 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+Nystatin+Sirolimus+Clotrimazole+Trimethoprim (TMP)/Sulfa (Bactrim, Septra)+Diphenhydramine+Alemtuzumab+Valgancyclovir+Methylprednisolone (or equivalent)+Tacrolimus+Pentamidine	淵鑰壓襯遞淵獵繭獵鬱(醖選積網繭觸艱膚憲廠) = 製築簾構選夢憲窪獵齋醖夢簾廠積夢範築淵窪 (鬱構簾繭構鏇窪鹹艱醖, 獵製簾願艱齋獵齋顧鹹 ~ 衊壓網鬱觸廠築範繭壓) 更多	-	2012-07-09
ASCO2006	N/A	肺孢子菌肺炎二线	100	Intravenous pentamidine	蓋醖淵醖餘範鬱顧艱顧(鬱壓餘構築齋簾鏇壓繭) = 餘積製構鹹觸願願鏇膚製獵憲膚繭獵襯獵簾醖 (構築餘製壓選選構繭範 )	-	2006-06-20