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)
1. Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R, Otto TD, Proto WR, Blagborough AM, Meister S, Wirjanata G et al.. (2015)
A novel multiple-stage antimalarial agent that inhibits protein synthesis.
Nature, 522 (7556): 315-20. [PMID:26085270]
2. Gilbert IH, Norcross N, Baragana Ruibal B, Porzelle A. (2013)
Anti-malarial agents.
Patent number: WO2013153357A1. Assignee: University Of Dundee. Priority date: 10/04/2012. Publication date: 17/10/2013.
3. McCarthy JS, Yalkinoglu Ö, Odedra A, Webster R, Oeuvray C, Tappert A, Bezuidenhout D, Giddins MJ, Dhingra SK, Fidock DA et al.. (2021)
Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.
Lancet Infect Dis, 21 (12): 1713-1724. [PMID:34715032]
4. Rottmann M, Jonat B, Gumpp C, Dhingra SK, Giddins MJ, Yin X, Badolo L, Greco B, Fidock DA, Oeuvray C et al.. (2020)
Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor.
Antimicrob Agents Chemother, 64 (4). [PMID:32041711]