Delving into the Latest Updates on Ferroquine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Hemozoin

Action

inhibitors

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-

Login to view timeline

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.

NCT03660839

/ CompletedPhase 2

A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:
To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor.
Secondary Objectives:
To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.
To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.
To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.
To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.
To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

Start Date11 Sep 2018

Sponsor / Collaborator

Sanofi

[+1]

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]

100 Clinical Results associated with Ferroquine

Login to view more data

100 Translational Medicine associated with Ferroquine

Login to view more data

100 Patents (Medical) associated with Ferroquine

Login to view more data

154

Literatures (Medical) associated with Ferroquine

01 Sep 2024·British Journal of Pharmacology

Topical application of a P2X2/P2X3 purine receptor inhibitor suppresses the bitter taste of medicines and other taste qualities

Article

Author: Breslin, Paul A. S. ; Ghidewon, Misgana Y. ; Jiang, Peihua ; Christensen, Carol M. ; Rivers, Natasha ; Tordoff, Michael G. ; Caronia, Lauren ; Flammer, Linda J. ; Ellis, Hillary

AbstractBackground and PurposeMany medications taste intensely bitter. The innate aversion to bitterness affects medical compliance, especially in children. There is a clear need to develop bitter blockers to suppress the bitterness of vital medications. Bitter taste is mediated by TAS2R receptors. Because different pharmaceutical compounds activate distinct sets of TAS2Rs, targeting specific receptors may only suppress bitterness for certain, but not all, bitter‐tasting compounds. Alternative strategies are needed to identify universal bitter blockers that will improve the acceptance of every medication. Taste cells in the mouth transmit signals to afferent gustatory nerve fibres through the release of ATP, which activates the gustatory nerve‐expressed purine receptors P2X2/P2X3. We hypothesized that blocking gustatory nerve transmission with P2X2/P2X3 inhibitors (e.g. 5‐(5‐iodo‐4‐methoxy‐2‐propan‐2‐ylphenoxy)pyrimidine‐2,4‐diamine [AF‐353]) would reduce bitterness for all medications and bitter compounds.Experimental ApproachHuman sensory taste testing and mouse behavioural analyses were performed to determine if oral application of AF‐353 blocks perception of bitter taste and other taste qualities but not non‐gustatory oral sensations (e.g. tingle).Key ResultsRinsing the mouth with AF‐353 in humans or oral swabbing it in mice suppressed the bitter taste and avoidance behaviours of all compounds tested. We further showed that AF‐353 suppressed other taste qualities (i.e. salt, sweet, sour and savoury) but had no effects on other oral or nasal sensations (e.g, astringency and oral tingle).Conclusion and ImplicationsThis is the first time a universal, reversible taste blocker in humans has been reported. Topical application of P2X2/P2X3 inhibitor to suppress bitterness may improve medical compliance.

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.

100 Deals associated with Ferroquine

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 2	Benin	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Kenya	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Gabon	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Cameroon	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Tanzania	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Burkina Faso	Sanofi	01 Oct 2009

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03660839 (Pubmed)	Phase 2	Malaria, Falciparum	140	400 mg ferroquine	fkpkwvcqtw(hjvjfktmvq) = Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively hyrsiqfpek (npkxwqpdnr ) View more	-	03 Jan 2023
				400 mg ferroquine plus artefenomel 300 mg
NCT02497612 (Pubmed \| Malar J) Manual	Phase 2	Malaria, Falciparum	373	artefenomel+ferroquine	(dkumzgvpxv) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg utalrsgxtn (gyfdkvkelg ) View more	Negative	19 May 2021
NCT03660839 (CTgov)	Phase 2	Malaria, Falciparum	140	Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 300 mg)	qgamqnwcid(fusimugryc) = vhfjmxcbqv cdbzosotss (buainypyfk, zeuetxkaex - cdectsvzxm) View more	-	02 Dec 2020
				Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 600 mg)	qgamqnwcid(fusimugryc) = qpmxpzzdwo cdbzosotss (buainypyfk, lvfrprcpyv - cafpofutil) View more
NCT02497612 (FALCI, CTgov)	Phase 2	Malaria, Falciparum	377	Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg))	yayqlgpojc(rzdxpoltjf) = pvpftccefb yuhdcronnr (utyaatvlnt, yfirbruexj - kpjeeybvii) View more	-	19 Oct 2020
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	yayqlgpojc(rzdxpoltjf) = rljnbsxhnm yuhdcronnr (utyaatvlnt, jdqeothrve - ewayeidvbn) View more
NCT00563914 (Pubmed \| Trans R Soc Trop Med Hyg \| Am J Trop Med Hyg) Manual	Phase 2	Malaria, Falciparum	72	Artesunate+Ferroquine	(kdnkttlsls) = mild increases（grade 1 toxicity）in ALT levels with a dose trend starting at 400 mg；two grade 2 ALT events（200 mg 1 pt，600 mg 1 pt） rdcigvsaww (lrwwiuxjit ) View more	Positive	01 Aug 2017
				Artesunate+Amodiaquine
NCT00988507 (Pubmed \| Lancet Infect Dis)	Phase 2	Malaria, Falciparum	326	Artesunate 4 mg/kg + Ferroquine 2 mg/kg	ufdboczfls(kadlmkumao) = dtgzecqezb dzslaqcoth (bsujwngozu, 90 - 100)	Positive	01 Dec 2015
				Artesunate 4 mg/kg + Ferroquine 4 mg/kg	ufdboczfls(kadlmkumao) = vlcumijcon dzslaqcoth (bsujwngozu, 93 - 100)