Delving into the Latest Updates on Artesunate/Mefloquine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AS/MQ, ASMQ, ASMQ FDC

+ [6]

Target

ATP2A1 x SERCA2

Action

inhibitors

Mechanism

ATP2A1 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 inhibitors), SERCA2 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Malaria, FalciparumMalaria

Inactive Indication-

Originator Organization

Fundação Oswaldo Cruz

Active Organization

Fundação Oswaldo Cruz

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

Brazil (01 Jan 2008),

Malaria

Regulation-

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Structure/Sequence

Molecular FormulaC17H17ClF6N2O

InChIKeyWESWYMRNZNDGBX-YLCXCWDSSA-N

CAS Registry51773-92-3

A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine + amodiaquine (AL+AQ) and artesunate- mefloquine+piperaquine (AS-MQ+PPQ) with the ACTs artemether-lumefantrine + placebo (AL+PBO) and artesunate- mefloquine + placebo (AS-MQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.

Start Date30 Jun 2021

Sponsor / Collaborator

University of Oxford

NCT03923725

/ RecruitingPhase 3IIT

A Multi-centre Randomised Controlled Non-inferiority Trial to Compare the Efficacy, Safety and Tolerability of Triple Artemisinin-based Combination Therapies Versus First-line ACTs + Placebo for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Africa

A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine+amodiaquine (AL+AQ) and artesunate-mefloquine+piperaquine (ASMQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (ASMQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.

Start Date01 Sep 2020

Sponsor / Collaborator

University of Oxford

ACTRN12622000638730

/ SuspendedPhase 2/3IIT

Clinical and parasitological efficacy of artesunate-amodiaquine over 28 days in the treatment of uncomplicated falciparum malaria in Cambodia

Start Date01 Jun 2020

Sponsor / Collaborator

National Center for Parasitology, Entomology and Malaria Control

100 Clinical Results associated with Artesunate/Mefloquine Hydrochloride

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100 Translational Medicine associated with Artesunate/Mefloquine Hydrochloride

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100 Patents (Medical) associated with Artesunate/Mefloquine Hydrochloride

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246

Literatures (Medical) associated with Artesunate/Mefloquine Hydrochloride

01 Feb 2024·Transactions of the Royal Society of Tropical Medicine and Hygiene

Artesunate-mefloquine therapy for uncomplicated Plasmodium falciparum malaria: an updated systematic review and meta-analysis of efficacy and safety

Review

Author: Peixoto, Henry Maia ; Pereira, Ana Carolina Esteves da Silva ; de Freitas, Beatriz Sales ; Fernandes, Gabriel Haiek

AbstractTo provide a continuous update on the safety and efficacy of artesunate-mefloquine (ASMQ) compared with other artemisinin combination therapy (ACT) schemes used in the treatment of uncomplicated malaria caused by Plasmodium falciparum, this study updated and expanded the results of the systematic literature review published in 2016. Only randomised controlled clinical trials published from 1 January 2001 to 12 June 2023 from five databases were included in this study. The results related to efficacy, expressed through RR, were summarized in meta-analyses, performed according to the compared ACTs and with the intention-to-treat and per-protocol analyses. The results related to safety were synthesized in a descriptive manner. Thirty-two studies were included, of which 24 had been analysed in the 2016 review and eight new ones were added. Although the methodological quality of most studies was considered moderate, the body of evidence gathered indicates that ASMQ continues to be safe and effective for the treatment of uncomplicated infections caused by P. falciparum compared with other ACTs. However, the inclusion of two new studies, which identified failure rates exceeding 10%, suggests a possible reduction in the efficacy of ASMQ in the analysed locations. The incidence of serious adverse effects, such as seizure, encephalopathy and cardiac arrhythmia, was infrequent in both the ASMQ group and the comparison groups. After including new evidence, ASMQ is still recommended as a first-line treatment of uncomplicated malaria caused by P. falciparum, although local aspects need to be considered.

01 Jan 2024·Life Science Alliance

APR-246 increases tumor antigenicity independent of p53

Article

Author: Zappasodi, Roberta ; Merghoub, Taha ; Zhong, Hong ; Ouerfelli, Ouathek ; George, Mariam M ; Stockwell, Brent R ; Thach, Daniel ; Zamarin, Dmitriy ; Venkatesh, Divya ; Liu, Cailian ; Wolchok, Jedd D ; Budhu, Sadna ; Liu, Hengrui ; Yao, Zhong-Ke ; Campesato, Luis Felipe ; Michels, Judith

We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate that APR-246 and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity of tumor cells directly. MQ treatment of murine B16F10 melanoma cells promoted activation of melanoma-specific CD8+T cells and increased the efficacy of a tumor cell vaccine using MQ-treated cells even when the B16F10 cells lacked p53. We then designed a novel combination of APR-246 with the TLR-4 agonist, monophosphoryl lipid A, and a CD40 agonist to further enhance these immunogenic effects and demonstrated a significant antitumor response. We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor’s p53 mutation status.

01 Nov 2023·The Journal of Clinical Hypertension

Muscle quality is negatively related to hypertension prevalence in adults: Results from NHANES 2011–2014

Article

Author: Zhu, Caiyan ; Bai, Xiaopeng ; Zhao, Jia ; Shi, Shuai ; Wang, Yufeng

AbstractResistance training could counter hypertension and improve muscle quality (MQ), but current evidence about the correlation between MQ and hypertension is limited. The authors aimed to explore this correlation using the data of participants aged 20–59 from NHANES 2011–2014 via a cross‐sectional study. The MQ was quantified as handgrip strength (kg)/lean soft tissue mass (kg) of the dominant arm. Weighted multivariate logistic regression models were mainly utilized to investigate the MQ—hypertension association; linear trend tests and subgroup analysis were also conducted. Moreover, the authors employed weighted multivariate linear regression models to uncover the association between blood pressure (BP) and MQ. Four thousand four hundred and sixty‐nine individuals were enrolled, and 1167 were hypertensive. Hypertensive participants had a lower MQ than normotensive participants. In the totally adjusted model, each unit elevation in MQ was related to a 7% reduction in hypertension prevalence (p =.002). There was a decreasing trend in hypertension prevalence and in systolic BP as the MQ increased from the bottom to the top quartile across all three models (p for trend ≤.01), with a 28% difference (OR: 0.72, 95% CI: 0.54, 0.95) in hypertension prevalence and a 1.88 mm Hg (95% CI: −3.56, −0.20) difference in SBP between the top and bottom quartiles in the fully adjusted model. Subgroup analysis further confirmed the MQ—hypertension inverse association. In conclusions, the MQ was negatively associated with hypertension prevalence and systolic BP, which suggests the MQ may be a protective factor for hypertension and need to be improved.

100 Deals associated with Artesunate/Mefloquine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Malaria, Falciparum	Brazil	-	08 May 2008
Malaria	Brazil	Fundação Oswaldo Cruz	01 Jan 2008

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Discovery	Senegal	-	-
Malaria, Falciparum	Discovery	Guinea	-	-
Malaria, Falciparum	Discovery	Malawi	-	-
Malaria, Falciparum	Discovery	Benin	-	-
Malaria, Falciparum	Discovery	Indonesia	-	-
Malaria, Falciparum	Discovery	Philippines	-	-
Malaria, Falciparum	Discovery	Côte d'Ivoire	-	-
Malaria, Falciparum	Discovery	Papua New Guinea	-	-
Malaria, Falciparum	Discovery	Chad	-	-
Malaria, Falciparum	Discovery	Kenya	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01708876 (Pubmed \| Clin Infect Dis)	Phase 3	Malaria, Vivax	103	Chloroquine	(zjrnqytzkb) = ggzzalwbze vmvfcowash (ezhmgepjhd, 46.8 - 75.6) View more	-	01 Jun 2016
				Artesunate-mefloquine	fftrekwdag(xzozvrfuuv) = ndvpmgepki wylukvkkrh (demxewjcgt ) View more
NCT01708876 (ACT KNOW, Pubmed \| Lancet Infect Dis)	Phase 3	Plasmodium knowlesi infection	252	Artesunate-mefloquine	fsrxbcpwde(latawnaihi) = bmfrorhjpf pofeiszhuw (jrobxyhchb ) View more	-	01 Feb 2016
				Chloroquine	fsrxbcpwde(latawnaihi) = ejuwebgexw pofeiszhuw (jrobxyhchb ) View more
NCT00373607 (Pubmed)	Phase 3	Malaria, Falciparum First line	522	mefloquine-artesunate	fsluqgaycu(zsexggrwsa) = nxqepnjowr ijnzxfsujk (omoztznezv ) View more	-	31 Oct 2007
				dihydroartemisinin-piperaquine	fsluqgaycu(zsexggrwsa) = xuptshnsrr ijnzxfsujk (omoztznezv ) View more