Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor-Reference-Cited by-同舟云学术

Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor

Published:2020-03-24 Issue:4 Volume:64 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Rottmann Matthias¹²,Jonat Brian³,Gumpp Christin¹²,Dhingra Satish K.⁴,Giddins Marla J.⁴,Yin Xiaoyan⁵,Badolo Lassina⁶,Greco Beatrice⁷,Fidock David A.⁴⁸,Oeuvray Claude⁷,Spangenberg Thomas⁷^ORCID

Affiliation:

1. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland

2. University of Basel, Basel, Switzerland

3. Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA

4. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA

5. Global Statistics for NDD, Immunology, Endocrinology, Fertility & Others, EMD Serono, Billerica, Massachusetts, USA

6. Discovery and Development Technologies, Merck Healthcare KGaA, Darmstadt, Germany

7. Global Health Institute of Merck, Eysins, Switzerland

8. Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA

Abstract

Antimalarial drug resistance in the Plasmodium falciparum parasite poses a constant challenge for drug development. To mitigate this risk, new antimalarial medicines should be developed as fixed-dose combinations. Assessing the pharmacodynamic interactions of potential antimalarial drug combination partners during early phases of development is essential in developing the targeted parasitological and clinical profile of the final drug product. Here, we have studied the combination of M5717, a P. falciparum translation elongation factor 2 inhibitor, and pyronaridine, an inhibitor of hemozoin formation.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02181-19

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