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

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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 LLCSanofi KK

Inactive Organization

Verlyx Pharma, Inc.

Drug Highest PhaseApproved

First Approval Date

US (16 Oct 1984),

Pneumonia, Pneumocystis

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC23H36N4O10S2

InChIKeyYBVNFKZSMZGRAD-UHFFFAOYSA-N

CAS Registry140-64-7

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

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100 Clinical Results associated with Pentamidine Isethionate

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100 Translational Medicine associated with Pentamidine Isethionate

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100 Patents (Medical) associated with Pentamidine Isethionate

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3,624

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

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 Mar 2025·Journal of Molecular and Engineering Materials

Molecular Docking and Ligand-Binding Analysis of Amidine Derivatives Targeting Pseudomonas aeruginosa and Escherichia coli Bacterial Strains: An In Silico Approach

Author: Rahim, Khoirul Solehah Abdul ; Aldaghri, Osamah ; Zango, Zakariyya Uba ; Algarawi, Maha ; Tong, Woei-Yenn ; Khoo, Kuan Shiong ; Eisa, M. H. ; Sulong, Nor Akmalyati ; Abidin, Asmaa Zainal ; Lim, Jun Wei ; Ibnaouf, Khalid H.

Gram-negative bacteria represent a formidable challenge due to their exhibition of elevated resistance to various antibiotics. This study delves into the crisis posed by antimicrobial resistance (AMR), focusing on the alarming rise of bacteria (Gram-negative), such as Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), notorious for their severe infections. By examining the binding interaction with antibiotics (ampicillin, ciprofloxacin, trimethoprim, pentamidine, furamidine, and oligoamidine) and bacterial protein targets, the study utilized molecular docking and ligand-binding analysis. The result reveals different LibDock scores with the bacterial strain. Higher scores indicate stronger binding. Pentamidine exhibited the highest scores with all bacterial strains. CDOCKER energy due to interaction was computed to analyze the molecules binding with the bacteria, and pentamidine stood with higher CDOCKER value, indicating strong binding affinity. The work also assessed the antibiotics likeness using the rule of Lipinski’s five (RO5), and several antibiotics conform to the criteria. Molecular dynamics simulations were conducted to estimate compound stabilities, revealing stable conformations. The results revealed a stable potential energy (PE) profile for 5V7A Chain B. The RMSD profiles exhibited deviations within certain time intervals, indicating potential conformational changes in the antibiotics.

01 Feb 2025·JOURNAL OF MOLECULAR STRUCTURE

Investigation of cytotoxic indoleninyl-thiobarbiturate zwitterions as DNA targeting agents

Author: Toh, Wen Xin ; Tan, Chun Hoe ; Lim, Siew Huah ; Sim, Kae Shin ; Ramle, Abdul Qaiyum ; Ng, Min Phin ; Lim, Ching Yi ; Funmi, Adebayo Zainab ; Tan, Yee Seng

A series of indoleninyl-thiobarbiturate zwitterions were synthesized in up to 83% yields from the Knoevenagel condensation between N-substituted diformyl indolenine and thiobarbiturate.The structures were characterized by spectroscopic methods such as NMR (1H, 13C), FT-IR, high-resolution mass spectrometry (HR-MS) and elemental anal.However, their physicochem. properties and biol. activities remain elusive.Herein, results from in silico ADMET calculations and cytotoxicity predictions suggest that all zwitterions are likely to exhibit a higher bioavailability and more specific cytotoxicity than doxorubicin.The notably high predicted cytotoxicity of 2d and drug-likeness score of 2f may be linked to the position of the fused benzene ring and methoxy groups, resp.The initial biol. assessment of these compounds began with in vitro DNA-binding studies because the treatment of numerous diseases such as cancer and bacterial infections is linked to DNA interactions.Zwitterion 2f demonstrated the most significant spectral change in DNA binding studies, suggesting a possible role of the methoxy group in inducing DNA binding activity.The hypothesis that 2f interacts with DNA through groove binding was confirmed by observations made during salt-back titration and DNA denaturation experimentsIt was anticipated that the non-zwitterionic 2f would interact more stably with DNA (PDB code: 453D) at the minor groove than its zwitterionic form based on mol. docking calculations and mol. dynamic (MD) simulations.Addnl., the MTT assay demonstrates that 2f is moderately cytotoxic to the human breast cancer cell line MDA-MD-231, most probably as a result of the previously stated DNA binding mechanisms.Overall, the computational and in vitro data suggest the potential application of 2f as a cytotoxic DNA-targeting agent.

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

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External Link

KEGG	Wiki	ATC	Drug Bank
D00834	Pentamidine Isethionate	P01CX01	DB00738

R&D Status

Approved

10 top approved records.

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

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
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
Hepatocellular Carcinoma	Phase 1	CA	Verlyx Pharma, Inc.	01 Aug 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03403621 (CTgov)	Phase 1/2	Cicatrix, Hypertrophic	6	Pentamidine Isethionate (Topical Pentamidine Isethionate)	lyyhdlwxmw(xvojsfmzeo) = iwuxispqkc nxetzxlqbu (exnobiecxd, dccaaqfrtd - tkpxaymqaa) View more	-	22 Nov 2023
NCT03403621 (CTgov)	Phase 1/2	Cicatrix, Hypertrophic	6	Placebo (Placebo Control)	lyyhdlwxmw(xvojsfmzeo) = rziqqoimtk nxetzxlqbu (exnobiecxd, nlmtnjhlwx - jqsqpxvmah) View more	-	22 Nov 2023
NCT01360762 (CTgov)	Phase 3	Acquired Immunodeficiency Syndrome \| Coinfection \| Leishmaniasis, Visceral	74	Pentamidine	vljyskudup(vuxcfgytcd) = dsmqeuxtyx qlfqjjawvf (zwpmbjyppv, xgywnbahcw - vtokjrgaey) View more	-	15 Feb 2019
Tandem Meetings ASTCT and CIBMTR2017	Not Applicable	Hematologic Neoplasms \| Pneumonia, Pneumocystis	-	IV Pentamidine	lkcdpxoayb(rncqeuqlye) = mthgrzpsyx euqkjlsmxv (chfmofctuc ) View more	-	01 Mar 2017
NCT00729807 (CTgov)	Phase 2	Refractory Melanoma \| Melanoma, Cutaneous Malignant	6	pentamidine	hzsibrgatv(tmdakpzjxe) = ypjvqaqhoj lnuliprwsu (ifutgksayi, velixvtxxh - wpagkufvtg) View more	-	21 Oct 2016
Tandem Meetings ASTCT and CIBMTR2016	Not Applicable	Pneumonia, Pneumocystis \| Hematopoietic stem cell transplantation	58	Intravenous Pentamidine	usmaxzvfoy(knlytaylka) = jvropdrzzs zuuqsnkvel (rzdmkrulqa )	Positive	01 Mar 2016
ARVO2013	Not Applicable	Acanthamoeba Keratitis	24	Pentamidine isethionate	nyymrfdgff(zjknqzeeat) = mlwyupxgre urpliluyjs (jinwhoprqg, 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	aohcmcpjaa(bpibxzonto) = pfjfqvjpxd wmaaxodsrb (kpiuxlxude, ddmmmpdjdt - vjcsmpclyt) 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	ewxlusaijw(lsbsjcbfie) = yycandkzfe zejbltglho (bwiglelbzm, ejshblrwoi - shupvmwejw) View more	-	09 Jul 2012
Tandem Meetings ASTCT and CIBMTR2012	Not Applicable	Hematopoietic stem cell transplantation	170	Intravenous Pentamidine	pzeogdvmel(tjgylxvikm) = iocvqapcfy ojejrvrwnh (unqrxmvhms ) View more	Positive	01 Feb 2012
ASCO2006	Not Applicable	Pneumonia, Pneumocystis Second line	100	Intravenous pentamidine	jccmschgzy(uovhrvpffm) = wyygzkgbcd dgwwqmhkeq (trbnbyuvej )	-	20 Jun 2006