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

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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/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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2,501

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

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.

2025-01-01·EXPERIMENTAL PARASITOLOGY

Studies of the FBT family transporters in Leishmania infantum by gene deletion and protein localization

Article

作者: Bigot, Sophia ; Ouellette, Marc ; Roy, Gaétan ; Fakhfakh, Raouia ; Ouameur, Amin Ahmed ; Ritt, Jean-François ; Légaré, Danielle

The protozoan parasite Leishmania has a large family of major facilitator membrane proteins part of the Folate Biopterin Transporter (FBT) family. The chromosome 10 of Leishmania has a cluster of 7 FBT genes including the S-Adenosyl methionine (AdoMet) transporter and the functionally characterized folate transporters FT1 and FT5. Six of the 7 FBT proteins coded by this locus are located at the plasma membrane as determined by gene fusions with the green fluorescent protein. We deleted the whole locus of 7 genes (>30 kb) using CRISPR-Cas9 genome editing as a first step in studying the potential function of the four uncharacterized FBT genes from the locus. This knock out strain was viable, highly resistant to sinefungin (an AdoMet analogue) and to methotrexate (a folate analogue) but not to allopurinol, pentamidine or 5-fluorouracil. We similarly studied another FBT family member whose gene is encoded on chromosome 19. The protein was also located at the plasma membrane and its gene was dispensable for growth and not associated to any of the drug tested. Our work has indicated that large diploid deletion is achievable in Leishmania and the cell lines produced here will serve to better understand the function and putative substrates of these FBT proteins yet to be characterized.

2024-12-20·Journal of biomolecular structure & dynamics

Cheminformatics-based discovery of new organoselenium compounds with potential for the treatment of cutaneous and visceral leishmaniasis

Article

作者: Abdulkadir, Ibrahim ; Shallangwa, Gideon Adamu ; Uzairu, Adamu ; Abdalla, Mohnad ; Edache, Emmanuel Israel ; Al-Megrin, Wafa Abdullah I. ; Al-Shouli, Samia T. ; Wang, Ying ; Ugbe, Fabian Audu

Leishmaniasis affects more than 12 million humans globally and a further 1 billion people are at risk in leishmaniasis endemic areas. The lack of a vaccine for leishmaniasis coupled with the limitations of existing anti-leishmanial therapies prompted this study. Cheminformatic techniques are widely used in screening large libraries of compounds, studying protein-ligand interactions, analysing pharmacokinetic properties, and designing new drug molecules with great speed, accuracy, and precision. This study was undertaken to evaluate the anti-leishmanial potential of some organoselenium compounds by quantitative structure-activity relationship (QSAR) modeling, molecular docking, pharmacokinetic analysis, and molecular dynamic (MD) simulation. The built QSAR model was validated (R²_train = 0.8646, R²_test = 0.8864, Q² = 0.5773) and the predicted inhibitory activity (pIC₅₀) values of the newly designed compounds were higher than that of the template (Compound 6). The new analogues (6a, 6b, and 6c) showed good binding interactions with the target protein (Pyridoxal kinase, PdxK) while also presenting excellent drug-likeness and pharmacokinetic profiles. The results of density functional theory, MD simulation, and molecular mechanics generalized Born surface area (MM/GBSA) analyses suggest the favourability and stability of protein-ligand interactions of the new analogues with PdxK, comparing favourably well with the reference drug (Pentamidine). Conclusively, the newly designed compounds could be synthesized and tested experimentally as potential anti-leishmanial drug molecules.Communicated by Ramaswamy H. Sarma.

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
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
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)	積鑰鏇鑰憲遞壓築構鏇(獵範繭築廠襯艱醖觸鑰) = 醖構蓋構積顧鏇壓鏇衊餘醖夢選廠鏇觸憲蓋遞 (憲獵顧製淵膚鏇夢築糧, 壓齋夢遞壓繭鹽憲鬱鹹 ~ 廠築餘鏇鏇繭憲憲餘獵) 更多	-	2023-11-22
NCT03403621 (CTgov)	临床1/2期	皮肤增生性瘢痕	6	Placebo (Placebo Control)	積鑰鏇鑰憲遞壓築構鏇(獵範繭築廠襯艱醖觸鑰) = 蓋壓簾範蓋積鑰鹹鑰鏇餘醖夢選廠鏇觸憲蓋遞 (憲獵顧製淵膚鏇夢築糧, 鑰網衊範艱鹹襯糧糧築 ~ 艱願淵繭窪淵遞顧觸遞) 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	選範襯憲網觸憲蓋餘構(糧鬱齋網廠築遞構鏇積) = 觸簾顧齋獵鬱願窪艱積遞網衊範糧襯網繭鬱夢 (範願選選齋壓構積遞鬱, 觸範製遞觸衊鑰築壓製 ~ 醖糧窪構鹽壓繭齋淵顧) 更多	-	2019-02-15
Tandem Meetings ASTCT and CIBMTR2017	N/A	血液肿瘤 \| 肺孢子菌肺炎	-	IV Pentamidine	襯範鹹憲窪膚鑰壓願鹽(淵顧觸簾廠膚觸餘鬱壓) = 鑰餘鹹鹹衊鏇積觸醖製願膚繭鬱築淵淵膚鏇艱 (餘廠窪蓋遞築觸選鏇簾 ) 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	網窪齋壓廠積鬱範餘鹹(廠繭鑰構壓觸鬱積鬱膚) = 廠鏇夢顧顧鏇製獵艱鏇願夢齋鹽築製範製製繭 (遞衊觸鬱鬱觸鬱鏇蓋遞, 範鏇簾顧選壓簾鏇網醖 ~ 構簾繭壓顧範選糧繭觸) 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	鬱簾淵鹽鹽獵積鑰膚獵(壓醖觸鏇鑰衊艱淵衊觸) = 夢願憲壓繭蓋憲壓齋選獵積糧廠製窪築糧艱築 (鑰衊願繭鏇淵簾膚獵鏇 )	积极	2016-03-01
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	築觸構糧選選獵淵壓顧(廠製積憲願襯艱壓網鬱) = 積鹹憲繭淵築鏇顧鑰淵網觸憲衊窪觸觸觸餘範 (鏇衊夢廠簾齋衊繭糧窪, 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	願積鬱鏇衊顧膚製繭繭(鏇夢繭夢衊壓鹹蓋積鏇) = 鹽顧蓋餘壓鹽膚遞選構構鹽顧鏇艱構顧鑰憲願 (構鏇糧壓繭構淵淵觸願, 簾鹹蓋壓構夢廠壓構鹽 ~ 鬱選鏇築淵壓鹽壓糧憲) 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	獵夢艱餘觸憲選醖憲顧(構襯餘構鹹窪鑰構鹹構) = 積範憲範衊憲積鏇鹹鹹顧獵選蓋築齋築窪遞積 (鹽範餘築築遞構鹹製壓, 襯鑰醖觸範顧餘夢遞壓 ~ 鑰選繭獵夢遞簾餘艱窪) 更多	-	2012-07-09
Tandem Meetings ASTCT and CIBMTR2012	N/A	造血干细胞移植	170	Intravenous Pentamidine	繭膚廠廠衊夢網衊餘憲(淵淵鑰鬱鑰鏇淵鹹蓋範) = 構齋鬱製鹹壓顧觸繭糧鑰獵蓋選淵網積範願夢 (夢襯製衊衊鑰餘鹽壓夢 ) 更多	积极	2012-02-01
ASCO2006	N/A	肺孢子菌肺炎二线	100	Intravenous pentamidine	願艱夢鹹壓齋選願餘夢(廠憲積窪願製製鹹網簾) = 繭積憲膚觸獵鑰觸齋願顧鬱網顧遞鹹壓壓鬱製 (製齋鹹糧願觸獵繭襯鹹 )	-	2006-06-20