M5717   

GtoPdb Ligand ID: 9737

Synonyms: DDD107498 | DDD498 | MMV121
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.
2D Structure
Click here for structure editor
Physico-chemical Properties
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
SMILES / InChI / InChIKey
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)
InChI Key BENUHBSJOJMZEE-UHFFFAOYSA-N
No information available.
Summary of Clinical Use
A first-in-human Phase I clinical trial of M5717 has been completed (NCT03261401, last update June, 2019).
Mechanism Of Action and Pharmacodynamic Effects
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