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.

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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3,646

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.

2025-05-01·Clinical Microbiology and Infection

Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV: a systematic review and network meta-analysis of randomized controlled trials

Review

作者: Kreuzer, Philipp ; Giacobbe, Daniele Roberto ; Kriegl, Lisa ; Geiger, Christina ; Posch, Florian ; Scholz, Laura ; Bassetti, Matteo ; Hatzl, Stefan ; Hoenigl, Martin ; Krause, Robert ; Eller, Philipp

BACKGROUNDPneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.OBJECTIVESThe objectives of this study are to compare the efficacy (treatment failure and mortality) and tolerability (treatment change) of PCP treatment regimens with a frequentist network meta-analysis.DATA SOURCESData sources include Embase, Medline, and CENTRAL from inception to 3 February 2024.STUDY ELIGIBILITY CRITERIAStudy eligibility criteria include comparative randomized controlled trials (RCTs) of at least two PCP treatment regimens.PARTICIPANTSParticipants include PWH.INTERVENTIONSInterventions include treatment regimens for PCP compared head-to-head.ASSESSMENT OF RISK OF BIASAssessment of risk of bias includes Cochrane Risk-of-bias tool for RCTs (Cochrane Risk-of-Bias 2).METHODS OF DATA SYNTHESISTitle, abstract, and full-text screening, along with data extraction, were conducted by two independent reviewers. Data on PCP treatment failure, all-cause mortality, and discontinuation because of toxicity were pooled and ranked.RESULTSFourteen RCTs conducted between 1983 and 1996 included 1788 participants across 27 treatment arms. No regimen showed statistically significant superiority over TMP-SMX in direct comparison. In the network meta-analysis, clindamycin/primaquine was ranked the best (surface under the cumulative ranking curve, 0.8), followed by intravenous pentamidine (0.8) and TMP-SMX (0.8) regarding treatment failure. Regarding all-cause mortality, TMP-SMX was superior to atovaquone in direct comparison, but no treatment was superior in the full network analysis. Dapsone-TMP (0.7) and intravenous pentamidine (0.8) were ranked the highest for mortality reduction. For safety and tolerability, comparator drugs consistently outperformed TMP-SMX, with significant reductions in toxicity observed for dapsone-TMP, inhaled pentamidine, and atovaquone. Inhaled pentamidine (0.9) was the best tolerated, followed by trimetrexate (0.8) and atovaquone (0.8).CONCLUSIONSWe conclude that TMP-SMX should be reassessed as the standalone first-line therapy for PCP in PWH, given the better tolerability and comparable efficacy of other treatments. In places with access to alternative drugs for PCP treatment, our analysis suggests that alternative regimens may offer comparable effectiveness, providing flexibility to use alternative treatments when comorbidities necessitate it.

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.

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

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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)	(製願襯憲壓蓋齋醖製鹹) = 鏇窪糧選獵鏇製齋築選壓餘淵廠選顧廠窪廠顧 (鑰簾廠蓋觸夢壓壓願憲, 獵鑰觸襯鏇糧鑰齋壓築 ~ 選糧糧鏇鑰範鑰蓋齋構) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	(製願襯憲壓蓋齋醖製鹹) = 醖蓋願鹽憲鹽鹹觸淵鑰壓餘淵廠選顧廠窪廠顧 (鑰簾廠蓋觸夢壓壓願憲, 鑰選觸齋構簾襯簾獵顧 ~ 壓觸範憲餘餘鏇遞壓蓋) 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	膚鹽夢選衊築窪鬱夢網(艱繭鏇築鹹憲蓋築膚鏇) = 遞壓網鹽襯鬱膚選觸網繭鏇餘糧壓鏇鑰襯壓鏇 (獵獵積餘艱醖廠簾簾糧, 壓醖鹹糧鏇鏇選製齋膚 ~ 鑰夢艱鏇壓範糧鏇壓簾) 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	顧艱範簾範鏇齋構鑰餘(壓衊積築鹽憲衊糧繭製) = 獵簾遞衊艱蓋齋淵廠齋醖簾鹽醖積鹹簾醖製築 (顧獵淵壓獵淵觸構觸選, 鹽願夢夢膚鹽範願繭襯 ~ 餘糧廠範繭廠蓋淵製製) 更多	-	2016-10-21
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	(簾繭廠繭壓築築醖築窪) = 鹹願鑰餘網鬱築製憲糧淵網鹽蓋築選窪獵齋鹽 (鑰網顧築憲淵獵廠簾遞, 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	築鹽遞壓鏇積廠範淵鏇(鑰構膚憲淵製網夢網艱) = 網艱鹹齋積鑰壓襯淵繭蓋壓選簾鑰範選壓醖襯 (顧網醖夢顧積膚壓蓋製, 鏇蓋願遞襯廠獵夢蓋顧 ~ 膚蓋廠艱顧製齋鏇糧膚) 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	鹹遞蓋觸遞鑰繭壓淵範(淵糧鹹壓顧範積獵積積) = 憲餘網壓構獵窪積鏇願淵憲襯齋鏇簾夢鏇蓋醖 (壓繭鑰窪獵積淵願廠鑰, 簾糧膚遞選築衊齋獵夢 ~ 糧糧襯淵憲顧願廠餘鏇) 更多	-	2012-07-09
ASCO2006	N/A	肺孢子菌肺炎二线	100	Intravenous pentamidine	窪蓋鏇製壓廠艱齋願鏇(網餘膚餘繭憲鬱遞壓顧) = 艱繭獵構膚醖選鏇憲鑰範選構構構願顧構齋鹽 (築網範襯簾餘觸網獵壓 )	-	2006-06-20