Delving into the Latest Updates on Cabamiquine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [6]

Target

PfeEF2

Mechanism

PfeEF2 inhibitors(P. falciparum translation elongation factor 2 inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

MalariaAcute MalariaMalaria, Falciparum

Inactive Indication-

Originator Organization

MMV Medicines for Malaria Venture

University Of Dundee

Active Organization

Merck Healthcare KGaAMerck Serono SA

Inactive Organization

Merck KGaA

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC27H31FN4O2

InChIKeyBENUHBSJOJMZEE-UHFFFAOYSA-N

CAS Registry1469439-69-7

This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data.

Start Date28 Nov 2023

Sponsor / Collaborator

Merck Healthcare KGaA

NCT05689047 / Active, not recruitingPhase 2

Phase IIa Proof of Concept, Multicenter, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 Plus Pyronaridine Administered Once Daily for 1 or 2 Days to Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)

The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria. Pyramax (Artesunate/Pyronaridine) will act as an internal control providing reference safety data and a benchmark for the efficacy evaluation.

Start Date29 Mar 2023

Sponsor / Collaborator

Merck Healthcare KGaA

NL-OMON49971 / CompletedNot Applicable

A Phase Ib, Randomized, Double-Blind, Placebo Controlled, Sequential Study of Single Oral Doses of M5717 to Explore the Chemoprophylactic Activity of M5717 in a Controlled Plasmodium falciparum Sporozoite Challenge Model in Healthy Participants - Chemoprophylactic Activity of M5717 in PfSPZ Challenge Model

Start Date08 Sep 2020

Sponsor / Collaborator

Merck & Co., Inc.

100 Clinical Results associated with Cabamiquine

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100 Translational Medicine associated with Cabamiquine

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100 Patents (Medical) associated with Cabamiquine

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24

Literatures (Medical) associated with Cabamiquine

08 Oct 2024·Antimicrobial Agents and Chemotherapy

A high content imaging assay for identification of specific inhibitors of native Plasmodium liver stage protein synthesis

Article

Author: Saeger, Sarah ; McLellan, James L. ; Morales-Hernandez, Beatriz ; Hanson, Kirsten K.

ABSTRACTPlasmodium parasite resistance to antimalarial drugs is a serious threat to public health in malaria-endemic areas. Compounds that target core cellular processes like translation are highly desirable, as they should be capable of killing parasites in their liver and blood stage forms, regardless of molecular target or mechanism. Assays that can identify these compounds are thus needed. Recently, specific quantification of native Plasmodium berghei liver stage protein synthesis, as well as that of the hepatoma cells supporting parasite growth, was achieved via automated confocal feedback microscopy of the o-propargyl puromycin (OPP)-labeled nascent proteome, but this imaging modality is limited in throughput. Here, we developed and validated a miniaturized high content imaging (HCI) version of the OPP assay that increases throughput, before deploying this approach to screen the Pathogen Box. We identified only two hits; both of which are parasite-specific quinoline-4-carboxamides, and analogs of the clinical candidate and known inhibitor of blood and liver stage protein synthesis, DDD107498/cabamiquine. We further show that these compounds have strikingly distinct relationships between their antiplasmodial and translation inhibition efficacies. These results demonstrate the utility and reliability of the P. berghei liver stage OPP HCI assay for the specific, single-well quantification of Plasmodium and human protein synthesis in the native cellular context, allowing the identification of selective Plasmodium translation inhibitors with the highest potential for multistage activity.

01 Aug 2024·Birth Defects Research

Absence of developmental and reproductive toxicity in rats, rabbits, and zebrafish embryos exposed to antimalarial drug cabamiquine

Article

Author: Tornesi, Belen ; Gado, Andreas ; Ballard, Peter ; Baeurle, Tobias Hyun Ho ; Spangenberg, Thomas ; Demarta‐Gatsi, Claudia ; Hewitt, Philip ; Oeuvray, Claude

AbstractBackgroundWhen developing new antimalarial drugs, considering their potential use during pregnancy as preventive or curative therapy is crucial. This prevents the parasite from affecting embryonic development and reduces maternal and fetal death risks. Consequently, understanding the exposure and safety of antimalarial drugs during pregnancy is crucial, with well‐designed animal studies playing a key role in this assessment.MethodsAs part of the drug development program for cabamiquine, a series of developmental and reproductive toxicity studies were conducted in rats and rabbits. Additionally, the zebrafish embryo model was used to further improve embryo exposure, minimize confounding factors related to maternal toxicity, and assess developmental risks of cabamiquine.ResultsIn these studies, although maternal toxicity was observed, there were no cabamiquine‐related adverse effects on fertility, embryonic, or fetal development at maternal exposures representing significant multiples (up to five and 10 times higher in rabbit and rats, respectively) than the exposure at the anticipated efficacious human dose. Similarly, no adverse effects were observed on ZF embryonic development, even though cabamiquine concentrations in the embryos were 10‐fold higher than nominal concentrations.ConclusionsThe results obtained in a full set of reproductive toxicity studies did not provide evidence of detrimental effects on the conceptuses and progeny at maternally nontoxic doses and exposures, still representing a multiple of the anticipated systemic exposures in women of childbearing potential (WOCBP). Cabamiquine can therefore be considered a suitable therapeutic option for WOCBP and pregnant women living in malaria‐endemic regions by significantly reducing maternal and infant malaria death rates.

01 Jun 2024·Life Science Alliance

Differential effects of translation inhibitors onPlasmodium bergheiliver stage parasites

Article

Author: Hanson, Kirsten K ; McLellan, James L

Increasing numbers of antimalarial compounds are being identified that converge mechanistically at inhibition of cytoplasmic translation, regardless of the molecular target or mechanism. A deeper understanding of how their effectiveness as liver stage translation inhibitors relates to their chemoprotective potential could prove useful. Here, we probed that relationship using thePlasmodium berghei–HepG2 liver stage infection model. After determining translation inhibition EC50s for five compounds, we tested them at equivalent effective concentrations to compare the parasite response to, and recovery from, a brief period of translation inhibition in early schizogony, followed by parasites to 120 h post-infection to assess antiplasmodial effects of the treatment. We show compound-specific heterogeneity in single parasite and population responses to translation inhibitor treatment, with no single metric strongly correlated to the release of hepatic merozoites for all compounds. We also demonstrate that DDD107498 is capable of exerting antiplasmodial effects on translationally arrested liver stage parasites and uncover unexpected growth dynamics during the liver stage. Our results demonstrate that translation inhibition efficacy does not determine antiplasmodial efficacy for these compounds.

100 Deals associated with Cabamiquine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria	Phase 2	GM	Merck Healthcare KGaA	28 Nov 2023
Malaria	Phase 2	ZM	Merck Healthcare KGaA	28 Nov 2023
Acute Malaria	Phase 2	BF	Merck Healthcare KGaA	29 Mar 2023
Acute Malaria	Phase 2	MZ	Merck Healthcare KGaA	29 Mar 2023
Acute Malaria	Phase 2	UG	Merck Healthcare KGaA	29 Mar 2023
Acute Malaria	Phase 2	GA	Merck Healthcare KGaA	29 Mar 2023
Malaria, Falciparum	Phase 2	UG	Merck Healthcare KGaA	29 Mar 2023
Malaria, Falciparum	Phase 2	MZ	Merck Healthcare KGaA	29 Mar 2023
Malaria, Falciparum	Phase 2	BF	Merck Healthcare KGaA	29 Mar 2023
Malaria, Falciparum	Phase 2	GA	Merck Healthcare KGaA	29 Mar 2023