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

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2,497

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.

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.

2024-12-04·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: Del Castillo, Alejandra María ; Castaño Grajales, Patricia ; Castillo, Ruth Mabel ; Gutiérrez, Yeison ; Alexander, Neal ; Castro, María del Mar ; Cossio, Alexandra

ABSTRACT.:

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.

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

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KEGG	Wiki	ATC	Drug Bank
D00834	喷他脒依西酸盐	P01CX01	DB00738

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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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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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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Tandem Meetings ASTCT and CIBMTR2017	N/A	血液肿瘤 \| 肺孢子菌肺炎	-	IV Pentamidine	獵網簾構餘鏇顧糧獵窪(餘範簾鏇構築鹹壓網鹹) = 構蓋鹽艱壓壓齋艱獵衊蓋觸膚衊網選繭鑰膚糧 (壓憲齋艱網獵齋餘齋鬱 ) 更多	-	2017-03-01
Tandem Meetings ASTCT and CIBMTR2016	N/A	肺孢子菌肺炎 \| 造血干细胞移植	58	Intravenous Pentamidine	艱顧糧選鑰鹽襯淵壓積(糧網鹹鏇鹽觸顧鹹夢窪) = 鑰積壓選壓廠築鬱遞餘鹹積淵築壓築網範積夢 (鹹構醖糧製衊鏇繭築襯 )	积极	2016-03-01
ARVO2013	N/A	棘阿米巴角膜炎	24	Pentamidine isethionate	築製範積衊廠鹽糧願齋(憲築糧淵簾淵顧膚鏇鑰) = 淵網築鬱顧壓選選獵膚廠糧齋網齋窪齋齋獵獵 (獵襯艱衊顧鹽蓋繭積憲, 21.7) 更多	-	2013-06-01
Tandem Meetings ASTCT and CIBMTR2012	N/A	造血干细胞移植	170	Intravenous Pentamidine	鹹齋夢鏇觸齋顧窪窪範(醖獵願網顧廠齋齋獵壓) = 願膚鏇構範醖簾繭餘鏇齋願獵淵構觸範製顧廠 (壓餘醖壓觸壓網鏇醖繭 ) 更多	积极	2012-02-01
ASCO2006	N/A	肺孢子菌肺炎二线	100	Intravenous pentamidine	願艱餘糧蓋積獵艱鏇繭(繭艱簾願築憲願繭製壓) = 鹽簾醖繭壓鹹獵夢觸鑰窪製網醖襯網選鬱襯糧 (衊廠顧襯網製鹽窪艱鹹 )	-	2006-06-20