Delving into the Latest Updates on Pentamidine Isethionate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1,5-bis(4-amidinophenoxy)pentane, 4,4'-(1,5-pentanediylbis(oxy))bis-benzenecarboximidamide, 4,4'-(pentamethylenedioxy)dibenzamidine

+ [18]

Target-

Mechanism-

Therapeutic Areas

Infectious DiseasesRespiratory DiseasesOther Diseases

Active Indication

Pneumonia, Pneumocystis

Inactive Indication

Hepatocellular CarcinomaMetastatic colon cancerMetastatic Colorectal Carcinoma+ [2]

Originator Organization

Fresenius Kabi AG

Active Organization

Fresenius Kabi USA LLC

Inactive Organization

Verlyx Pharma, Inc.

Drug Highest PhaseApproved

First Approval Date

US (16 Oct 1984),

Pneumonia, Pneumocystis

RegulationOrphan Drug (US)

Login to view timeline

Structure/Sequence

Molecular FormulaC19H24N4O2

InChIKeyXDRYMKDFEDOLFX-UHFFFAOYSA-N

CAS Registry100-33-4

View All Structures (2)

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

Start Date19 Dec 2018

Sponsor / Collaborator

University of Kentucky

NCT03403621

/ TerminatedPhase 1/2IIT

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.

Start Date05 Mar 2018

Sponsor / Collaborator

Mayo Clinic

NCT03201159

/ WithdrawnPhase 1IIT

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.

Start Date25 Jun 2017

Sponsor / Collaborator

National Institute on Alcohol Abuse & Alcoholism

[+3]

100 Clinical Results associated with Pentamidine Isethionate

Login to view more data

100 Translational Medicine associated with Pentamidine Isethionate

Login to view more data

100 Patents (Medical) associated with Pentamidine Isethionate

Login to view more data

2,568

Literatures (Medical) associated with Pentamidine Isethionate

01 Apr 2025·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

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

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.

01 Feb 2025·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

Author: 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.

01 Jan 2025·Experimental Parasitology

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

Article

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

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.

1

News (Medical) associated with Pentamidine Isethionate

07 Mar 2024

·www.businesswire.com

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 .

AACRClinical Result

100 Deals associated with Pentamidine Isethionate

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D00834	Pentamidine Isethionate	P01CX01	DB00738

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Pneumonia, Pneumocystis	US	Fresenius Kabi USA LLC	16 Oct 1984

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 2	CA	Verlyx Pharma, Inc.	01 Aug 2014
metastatic non-small cell lung cancer	Phase 2	PL	Verlyx Pharma, Inc.	01 Sep 2012
Metastatic Colorectal Carcinoma	Phase 2	CA	Verlyx Pharma, Inc.	01 Mar 2011
Pancreatic Cancer	Phase 2	CA	Verlyx Pharma, Inc.	01 Jan 2009
Metastatic colon cancer	Phase 2	CA	Verlyx Pharma, Inc.	01 Mar 2008

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03403621 (CTgov)	Phase 1/2	Cicatrix, Hypertrophic	6	Pentamidine Isethionate (Topical Pentamidine Isethionate)	(rhjwxaeoru) = dlektwwgaw vvfysxsrmp (nztvauoluj, kcdrowgtar - xcqoaigtfs) View more	-	22 Nov 2023
NCT03403621 (CTgov)	Phase 1/2	Cicatrix, Hypertrophic	6	Placebo (Placebo Control)	(rhjwxaeoru) = xxfbolbyoo vvfysxsrmp (nztvauoluj, wryjcgokmu - bcchpqddan) View more	-	22 Nov 2023
NCT01360762 (CTgov)	Phase 3	Acquired Immunodeficiency Syndrome \| Coinfection \| Leishmaniasis, Visceral	74	Pentamidine	ygzfbazldf(eyzgbzleca) = bvcbywwtuj cthmlpbqbb (ztzcgfxbal, mullrttiog - egqidziiuk) View more	-	15 Feb 2019
NCT00729807 (CTgov)	Phase 2	Refractory Melanoma \| Melanoma, Cutaneous Malignant	6	pentamidine	orrwiqchzp(xbupjqgync) = bqpgtermea tonigirdkw (umxrtoiorp, iqoimhyrtc - oiydfnsxge) View more	-	21 Oct 2016
ARVO2013	Not Applicable	Acanthamoeba Keratitis	24	Pentamidine isethionate	(htklmjdjod) = lvhioohlzh kikgtatabe (bmuepmhhqc, 21.7) View more	-	01 Jun 2013
NCT00014911 (CTgov)	Phase 2	Diabetes Mellitus, Type 1	36	Islet Transplantation+Ganciclovir+Sulfamethoxazole+Tacrolimus+Sirolimus+Daclizumab+Pentamidine+Trimethoprim	dgglcrexvc(rgferykgim) = eafcnsxtbe ymdchgjtvd (wiksdyjajq, kxneieeasa - fgumpfdzqi) View more	-	17 Oct 2012
NCT00078559 (CTgov)	Phase 1/2	Kidney Diseases \| Renal transplant rejection	10	Kidney transplant+Acyclovir+Acetaminophen+Nystatin+Sirolimus+Clotrimazole+Trimethoprim (TMP)/Sulfa (Bactrim, Septra)+Diphenhydramine+Alemtuzumab+Valgancyclovir+Methylprednisolone (or equivalent)+Tacrolimus+Pentamidine	uwuiczweva(lyshwuymja) = wsterzwsgs izwlkksxxv (wulkitotpp, vofmgwsroa - vsupnbikng) View more	-	09 Jul 2012
ASCO2006	Not Applicable	Pneumonia, Pneumocystis Second line	100	Intravenous pentamidine	wqsmnfqlqn(tfexlcgckk) = gllqxqbfdk fokeplrilo (dbzvujyczi )	-	20 Jun 2006