M5717   Click here for help

GtoPdb Ligand ID: 9737

Synonyms: DDD107498 | DDD498 | MMV121
Antimalarial Ligand
Compound class: Synthetic organic
Comment: M5717 (formerly DDD498) is a quinoline-4-carboxamide derivative that is the optimised lead developed from a phenotypic screen for novel antimalarial drugs and has advanced to clinical evaluation. The compound was awarded MMV Project of the Year (2014).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 57.7
Molecular weight 462.24
XLogP 3.43
No. Lipinski's rules broken 0
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Canonical SMILES Fc1ccc2c(c1)c(cc(n2)c1ccc(cc1)CN1CCOCC1)C(=O)NCCN1CCCC1
Isomeric SMILES Fc1ccc2c(c1)c(cc(n2)c1ccc(cc1)CN1CCOCC1)C(=O)NCCN1CCCC1
InChI InChI=1S/C27H31FN4O2/c28-22-7-8-25-23(17-22)24(27(33)29-9-12-31-10-1-2-11-31)18-26(30-25)21-5-3-20(4-6-21)19-32-13-15-34-16-14-32/h3-8,17-18H,1-2,9-16,19H2,(H,29,33)
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Summary of Clinical Use Click here for help
M5717 has completed first-in-human (NCT03261401, last update June 2019) and human challenge (NCT04250363, last update July 2021) Phase 1 clinical trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
M5717 inhibits P. falciparum protein synthesis, with evidence from genetic experiments indicating P. falciparum elongation factor 2 (PfeEF2) may be the molecular target [1]. eEF2 catalyzes the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis in eukaryotes.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03261401 First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Subjects Phase 1 Interventional Merck KGaA, Darmstadt, Germany 3
NCT04250363 Chemoprophylactic Activity of M5717 in Plasmodium Falciparum Sporozoite (PfSPZ) Challenge Model Phase 1 Interventional Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Pharmacokinetics Click here for help
The mean terminal half-life for elimination ranged from 155 to 193 hours in human volunteers [4].