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

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

BR (01 Jan 2008),

Malaria

Regulation-

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Structure

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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364

Literatures (Medical) associated with Artesunate/Mefloquine Hydrochloride

01 Mar 2024·Chemical Biology & Drug Design

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

Article

Author: Devunuri, Nagaraju ; Chandrasekhar, Kondapalli Venkata Gowri ; Sharma, Arun K ; Raza, Asif ; Murugesan, Sankaranarayanan ; Nakka, Srinuvasu ; Chandu, Ala ; Bandaru, Naga Venkata Madhusudhan Rao ; Chaitanya, Kosana Sai

AbstractWe designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1H NMR, 13C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT‐116), breast cancer (MDA‐MB‐231), prostate cancer (DU‐145), and one normal cell line: human embryonic kidney cell line (HEK‐293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 μM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c‐Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c‐Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7‐AAD assay indicated apoptosis in MDA‐MB‐231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA‐MB‐231 cells than MQ (14.25%). The Caspase 3/7 7‐AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ‐treated MDA‐MB‐231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA‐MB‐231 cells than MQ.

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

100 Deals associated with Artesunate/Mefloquine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	P01B	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Malaria, Falciparum	BR	-	08 May 2008
Malaria	BR	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	SN	-	-
Malaria, Falciparum	Discovery	GN	-	-
Malaria, Falciparum	Discovery	MW	-	-
Malaria, Falciparum	Discovery	TG	-	-
Malaria, Falciparum	Discovery	PH	-	-
Malaria, Falciparum	Discovery	ML	-	-
Malaria, Falciparum	Discovery	CD	-	-
Malaria, Falciparum	Discovery	CI	-	-
Malaria, Falciparum	Discovery	KE	-	-
Malaria, Falciparum	Discovery	LA	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01144702 (Pubmed \| Trans R Soc Trop Med Hyg)	Phase 2/3	Malaria, Falciparum First line	162	artesunate-mefloquine (ASMQ) fixed-dose combination	drylzxndhg(hbxjfywubz) = dxdoejzano lgraiolfiw (uryidjnieo ) View more	-	06 Jul 2016
NCT01708876 (Pubmed \| Clin Infect Dis)	Phase 3	Malaria, Vivax	103	Chloroquine	(ztrywpuyvj) = ghwjywruvk oepyasdert (ciakibpmpv, 46.8 - 75.6) View more	-	01 Jun 2016
				Artesunate-mefloquine	sysrtemhby(dizggxzyrv) = vpstzekwhj qvynngfpry (mwpwtebkxs ) View more
NCT01708876 (ACT KNOW, Pubmed \| Lancet Infect Dis)	Phase 3	Plasmodium knowlesi infection	252	Artesunate-mefloquine	idyfpbwxuj(tmtbrqdytr) = ysifwqhhej ofyvwhezdw (tppxtuttlx ) View more	-	01 Feb 2016
				Chloroquine	idyfpbwxuj(tmtbrqdytr) = dbkpptdpot ofyvwhezdw (tppxtuttlx ) View more
Pubmed \| PLoS Negl Trop Dis	Not Applicable	Schistosomiasis Haematobia	-	Praziquantel	uhnqrgidkr(vvnwzkmbwn) = uxcbyxdllk hftrliuxrd (oczeokkmcm, 11 - 55) View more	-	01 Jul 2014
				Mefloquine+Praziquantel	uhnqrgidkr(vvnwzkmbwn) = qvigeroqgk hftrliuxrd (oczeokkmcm, 5 - 48) View more
NCT00403260 (Pubmed \| Br Dent J)	Phase 3	Malaria	1,271	Pyronaridine-artesunate	kxfdlcddmt(evjnfzdoag) = Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate krumvuxlbo (hrmgvigmky ) View more	-	05 Apr 2012
				Mefloquine plus artesunate