Delving into the Latest Updates on Ferroquine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Hemozoin

Mechanism

Hemozoin inhibitors

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Malaria, Falciparum

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H24ClFeN3

InChIKeyDDENDDKMBDTHAX-UHFFFAOYSA-N

CAS Registry185055-67-8

Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Plasmodium falciparum can lead to severe malaria and accounts for 90% of malaria deaths that mainly occur in children below the age of 5 years in Sub-Saharan Africa.
A simplified treatment regimen, ideally a single-day cure (or at most 2-day dosing regimen), of uncomplicated malaria due to P. falciparum would be the magic in the antimalarial armamentarium. Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also the transmission of malaria, and such a regimen would substantially increase adherence. To find a new non-artemisinin combination therapy with a shorter regimen, ideally, a single-dose cure, with low resistance potential would be the aim. The two compounds tested here are ZY19489, a triaminopyrimidine, and ferroquine (FQ), a next-generation 4-aminoquinoline. Both compounds show unique features in terms of long half-life, and activity against current drug-resistant strains.
Therefore, the main goal of this clinical trial is to assess the safety of the ZY19489-FQ combination given as a 1- or 2-day dose regimen.

Start Date30 Aug 2024

Sponsor / Collaborator

Zydus Lifesciences Ltd.

NCT02497612

/ TerminatedPhase 2

A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:
To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.
Secondary Objectives:
To evaluate the efficacy of OZ439/FQ:
To determine the incidence of recrudescence and re-infection.
To determine the time to relief of fever and parasite clearance.
To evaluate the safety and tolerability of OZ439/FQ in adults and children.
To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood.
To determine the blood/plasma ratio for FQ and SSR97213 in some participants at limited time points in selected sites.

Start Date25 Jul 2015

Sponsor / Collaborator

Sanofi

[+1]

ACTRN12613001040752

/ CompletedPhase 2IIT

An experimental study to characterize the effectiveness of ferroquine against early Plasmodium falciparum blood stage infection in healthy volunteers

Start Date17 Oct 2013

Sponsor / Collaborator

QIMR Berghofer Medical Research Institute

100 Clinical Results associated with Ferroquine

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100 Translational Medicine associated with Ferroquine

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100 Patents (Medical) associated with Ferroquine

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87

Literatures (Medical) associated with Ferroquine

01 Aug 2024·Bioorganic Chemistry

Exploring antimalarial potential: Conjugating organometallic moieties with organic fragments for enhanced efficacy

Review

Author: Hafizah Mukhtar, Nur ; Suhaily Saaidin, Aimi ; Huda Abd Karim, Nurul ; Ismail, Norzila ; Yee Ling, Lau ; Ebihara, Masahiro ; Aqilah Zahirah Norazmi, Nur ; Ravindar, Lekkala ; Kartini Agustar, Hani ; Hamizah Ali, Amatul ; Izzaty Hassan, Nurul

In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.

01 Jul 2024·The Chemical Record

Ferrocenyl Azoles: Versatile N‐Containing Heterocycles and their Anticancer Activities

Review

Author: Sadanala, Bhavya Deepthi ; Trivedi, Rajiv

AbstractThe medicinal chemistry of ferrocene has gained its momentum after the discovery of biological activities of ferrocifen and ferroquine. These ferrocenyl drugs have been designed by replacing the aromatic moiety of the organic drugs, tamoxifen and chloroquine respectively, with a ferrocenyl unit. The promising biological activities of these ferrocenyl drugs have paved a path to explore the medicinal applications of several ferrocenyl conjugates. In these conjugates, the ferrocenyl moiety has played a vital role in enhancing or imparting the anticancer activity to the molecule. The ferrocenyl conjugates induce the cytotoxicity by generating reactive oxygen species and thereby damaging the DNA. In medicinal chemistry, the five membered nitrogen heterocycles (azoles) play a significant role due to their rigid ring structure and hydrogen bonding ability with the biomolecules. Several potent drug candidates with azole groups have been in use as chemotherapeutics. Considering the importance of ferrocenyl moiety and azole groups, several ferrocenyl azole conjugates have been synthesized and screened for their biological activities. Hence, in the view of a wide scope in the development of potent drugs based on ferrocenyl azole conjugates, herein we present the details of synthesis and the anticancer activities of ferrocenyl compounds bearing azole groups such as imidazole, triazoles, thiazole and isoxazoles.

08 Mar 2024·ACS Infectious Diseases

Antifungal and Antiparasitic Activities of Metallocene-Containing Fluconazole Derivatives

Article

Author: Mitreva, Makedonka ; Gambino, Dinorah ; Ballesteros-Casallas, Andres ; Salinas, Gustavo ; Weil, Tobias ; Vinck, Robin ; Gasser, Gilles ; Cariou, Kevin ; Blacque, Olivier ; Scalese, Gonzalo ; Pérez Díaz, Leticia ; Sakanari, Judy A ; Bulman, Christina A ; Lin, Yan ; Paulino, Margot

The search for new anti-infectives based on metal complexes is gaining momentum. Among the different options taken by researchers, the one involving the use of organometallic complexes is probably the most successful one with a compound, namely, ferroquine, already in clinical trials against malaria. In this study, we describe the preparation and in-depth characterization of 10 new (organometallic) derivatives of the approved antifungal drug fluconazole. Our rationale is that the sterol 14α-demethylase is an enzyme part of the ergosterol biosynthesis route in Trypanosoma and is similar to the one in pathogenic fungi. To demonstrate our postulate, docking experiments to assess the binding of our compounds with the enzyme were also performed. Our compounds were then tested on a range of fungal strains and parasitic organisms, including the protozoan parasite Trypanosoma cruzi (T. cruzi) responsible for Chagas disease, an endemic disease in Latin America that ranks among some of the most prevalent parasitic diseases worldwide. Of high interest, the two most potent compounds of the study on T. cruzi that contain a ferrocene or cobaltocenium were found to be harmless for an invertebrate animal model, namely, Caenorhabditis elegans (C. elegans), without affecting motility, viability, or development.

100 Deals associated with Ferroquine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 2	BJ	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	KE	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	GA	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	CM	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	BF	Sanofi	01 Oct 2009
Malaria, Falciparum	Preclinical	TZ	Sanofi	01 Oct 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02497612 (Pubmed \| Malar J) Manual	Phase 2	Malaria, Falciparum	373	artefenomel+ferroquine	(sfuhckijxw) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg qgxscbqtjj (misrbxxtnn ) View more	Negative	19 May 2021
NCT02497612 (FALCI, CTgov)	Phase 2	Malaria, Falciparum	377	Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg))	zhbnfxgyde(xudtwkvnlq) = vqpkkrrokd mcyzaeibxr (zosjdaoxaw, zhmddklfkb - ckvuzpnhka) View more	-	19 Oct 2020
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	zhbnfxgyde(xudtwkvnlq) = nvyirgqedn mcyzaeibxr (zosjdaoxaw, lfmgsoolfw - egxwowcihj) View more
NCT00988507 (Pubmed \| Lancet Infect Dis)	Phase 2	Malaria, Falciparum	326	Artesunate 4 mg/kg + Ferroquine 2 mg/kg	oxuyqtgcst(sfeoddstsl) = vmnlsomtjs hzktqohxfl (iygzkdozjg, 90 - 100)	Positive	01 Dec 2015
				Artesunate 4 mg/kg + Ferroquine 4 mg/kg	oxuyqtgcst(sfeoddstsl) = pfruhlisiq hzktqohxfl (iygzkdozjg, 93 - 100)