Delving into the Latest Updates on Melarsoprol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Melarsoprol (INN)

+ [3]

Target

PKLR x PKM2

Action

modulators

Mechanism

PKLR modulators(Pyruvate kinase isozymes R/L modulators), PKM2 modulators(Pyruvate kinase isozymes M1/M2 modulators)

Therapeutic Areas

Infectious Diseases

Active Indication

Trypanosomiasis

Inactive Indication-

Originator Organization

Sanofi-Aventis France SA

Active Organization

Sanofi-Aventis France SA

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

France (02 May 1997),

Trypanosomiasis

RegulationOrphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC12H15AsN6OS2

InChIKeyJCYZMTMYPZHVBF-UHFFFAOYSA-N

CAS Registry494-79-1

The treatment human African trypanosomiasis (HAT) in the meningoencephalitic phase relies on two molecules officially registered: melarsoprol, the most commonly used, has a poor safety profile and is becoming ineffective due to parasite resistance; and eflornithine, with better tolerance but more complicated and expensive to implement in endemic countries. nifurtimox, registered only for Chagas' disease but used off-label since the 1970's in series of cases of HAT, is at present the only other available alternative.
The very limited number of compounds available, the lack of prospects for the development of new products and the emergence of resistance are arguments for the use of therapeutic combinations.
This study evaluates the efficacy and safety of three drug combination therapies: melarsoprol-nifurtimox, melarsoprol-eflornithine and eflornithine-nifurtimox.

Start Date01 Mar 2001

Sponsor / Collaborator

Médecins Sans Frontières

100 Clinical Results associated with Melarsoprol

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100 Translational Medicine associated with Melarsoprol

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100 Patents (Medical) associated with Melarsoprol

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586

Literatures (Medical) associated with Melarsoprol

13 Mar 2025·Clinical Microbiology Reviews

Transforming the chemotherapy of human African trypanosomiasis

Review

Author: Barrett, Michael P.

SUMMARY Prior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the Trypanosoma brucei parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement. Prior to 2019, different drugs were required for each of the two parasite sub-species at each stage. Gambiense disease required pentamidine or nifurtimox-eflornithine combination therapy, while for rhodesiense disease, suramin or melarsoprol was given for stages 1 and 2, respectively. These drugs all suffered complications including protracted administration regimens involving multiple injections with drug-induced adverse effects common. Today, a single drug, fexinidazole, can be given orally in most cases for both diseases at either stage. Another compound, acoziborole, effective in both stages 1 and 2 gambiense disease with a single dosing is anticipated to become available within a few years. Moreover, the recent engagement of multilateral organizations in seeking other compounds that could be used in HAT therapy has also been successful, and a rich vein of new trypanocides has been discovered. Here, the clinical use, modes of action, and resistance risks for drugs used against HAT are discussed.

01 Feb 2025·The Lancet Infectious Diseases

New WHO guidelines for treating rhodesiense human African trypanosomiasis: expanded indications for fexinidazole and pentamidine

Review

Author: Mesha, Tihitina ; Lindner, Andreas K ; Pasi, Christopher ; Villanueva, Gemma ; Barrett, Michael P ; Kadima Ebeja, Augustin ; Blumberg, Lucille ; Simarro, Pere P ; Chancey, Rebecca J ; Priotto, Gerardo ; Lejon, Veerle ; Bukachi, Salome A ; Probyn, Katrin ; Matemba, Lucas ; Franco, Jose R ; Akl, Elie A ; Edielu, Andrew ; Seixas, Jorge ; Mwanakasale, Victor ; Phiri, Tapunda

Human African trypanosomiasis is a neglected tropical disease that is usually fatal without treatment. WHO has revised its rhodesiense human African trypanosomiasis treatment guidelines on the basis of an independent systematic literature review and following the GRADE methodology. This Review reports on the decision-making process and summarises the new recommendations and their potential implications for health-care professionals and policy makers. Due to data scarcity, all recommendations are conditional and based on very low certainty of evidence. Fexinidazole replaces suramin and melarsoprol as the first-line therapy in individuals aged 6 years and older with a bodyweight of 20 kg or more. As fexinidazole is effective in both stages of rhodesiense human African trypanosomiasis, a lumbar puncture for staging is no longer required. In settings in which first-choice drugs are not readily available, immediate interim treatment with pentamidine is suggested. The introduction of oral fexinidazole represents an advancement in the management of rhodesiense human African trypanosomiasis considering the life-threatening adverse reactions individuals can have to melarsoprol. However, children below the age or weight limits remain ineligible for treatment with fexinidazole.

01 Feb 2025·Current Computer-Aided Drug Design

Insights to Design New Drugs against Human African Trypanosomiasis Targeting Rhodesain using Covalent Docking, Molecular Dynamics Simulations, and MM-PBSA Calculations

Article

Author: dos Santos Nascimento, Igor José ; Santos, Mirelly Barbosa ; de Moura, Ricardo Olimpio ; De Jesus Marinho, Washley Phyama

Background:Neglected tropical diseases (NTDs) are parasitic and bacterial diseases that affect approximately 149 countries, mainly the poor population without basic sanitation. Among these, Human African Trypanosomiasis (HAT), known as sleeping sickness, shows alarming data, with treatment based on suramin and pentamidine in the initial phase and melarsoprol and eflornithine in the chronic phase. Thus, to discover new drugs, several studies point to rhodesain as a promising drug target due to the function of protein degradation and intracellular transport of proteins between the insect and host cells and is present in all cycle phases of the parasite.Methods:Here, based on the previous studies by Nascimento et al. (2021) [5], that show the main rhodesain inhibitors development in the last decade, molecular docking and dynamics were applied in these inhibitors datasets to reveal crucial information that can be into drug design.Results:Also, our findings using MD simulations and MM-PBSA calculations confirmed Gly19, Gly23, Gly65, Asp161, and Trp184, showing high binding energy (ΔGbind between -72.782 to -124.477 kJ.mol-1). In addition, Van der Waals interactions have a better contribution (-140,930 to -96,988 kJ.mol-1) than electrostatic forces (-43,270 to -6,854 kJ.mol-1), indicating Van der Waals interactions are the leading forces in forming and maintaining ligand-rhodesain complexes. Thus, conventional and covalent docking was employed and highlighted the presence of Michael acceptors in the ligands in a peptidomimetics scaffold, and interaction with Gly19, Gly23, Gly65, Asp161, and Trp184 is essential to the inhibiting activity. Furthermore, the Dynamic Cross-Correlation Maps (DCCM) show more correlated movements for all complexes than the free rhodesain and strong interactions in the regions of the aforementioned residues. Principal Component Analysis (PCA) demonstrates complex stability corroborating with RMSF and RMSD.Conclusion:This study can provide valuable insights that can guide researchers worldwide to discover a new promising drug against HAT.

100 Deals associated with Melarsoprol

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External Link

KEGG	Wiki	ATC	Drug Bank
D00832	Melarsoprol	P01CD01	DB12864

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Trypanosomiasis	France	Sanofi-Aventis France SA	02 May 1997

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISRCTN40537886 (Pubmed \| PLoS Negl Trop Dis)	Not Applicable	Trypanosomiasis, African	-	10-day melarsoprol schedule	rcwvfezptu(gpgskdtahr) = vmbnnaqvif dnpnuwahoa (lfvvilzbcg, 3 - 13.8) View more	-	01 Aug 2012
				melarsoprol (historic controls)	rcwvfezptu(gpgskdtahr) = bkqnmqseen dnpnuwahoa (lfvvilzbcg, 6 - 12.6) View more
ASCO2011	Not Applicable	Multiple Myeloma	-	MEL on day -2	ukprasdqxc(njremerqxt) = inbpkbqrdn lwznmudoth (kohgejpfpx ) View more	-	20 May 2011
				MEL on day -1	ukprasdqxc(njremerqxt) = ivayaftymk lwznmudoth (kohgejpfpx ) View more