Compound class:
Synthetic organic
Comment: DSM265 is an optimised candidate and clinical lead from the triazolopyrimidine structural class and represents a new class of antimalarial drug [1].
The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY. Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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References |
1. Coteron JM, Marco M, Esquivias J, Deng X, White KL, White J, Koltun M, El Mazouni F, Kokkonda S, Katneni K et al.. (2011)
Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential. J Med Chem, 54 (15): 5540-61. [PMID:21696174] |
2. Kokkonda S, Deng X, White KL, El Mazouni F, White J, Shackleford DM, Katneni K, Chiu FCK, Barker H, McLaren J et al.. (2020)
Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria. J Med Chem, 63 (9): 4929-4956. [PMID:32248693] |
3. Llanos-Cuentas A, Casapia M, Chuquiyauri R, Hinojosa JC, Kerr N, Rosario M, Toovey S, Arch RH, Phillips MA, Rozenberg FD et al.. (2018)
Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study. Lancet Infect Dis, 18 (8): 874-883. [PMID:29909069] |
4. McCarthy JS, Lotharius J, Rückle T, Chalon S, Phillips MA, Elliott S, Sekuloski S, Griffin P, Ng CL, Fidock DA et al.. (2017)
Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study. Lancet Infect Dis, 17 (6): 626-635. [PMID:28363636] |
5. Phillips MA, Lotharius J, Marsh K, White J, Dayan A, White KL, Njoroge JW, El Mazouni F, Lao Y, Kokkonda S et al.. (2015)
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci Transl Med, 7 (296): 296ra111. [PMID:26180101] |
6. Sulyok M, Rückle T, Roth A, Mürbeth RE, Chalon S, Kerr N, Samec SS, Gobeau N, Calle CL, Ibáñez J et al.. (2017)
DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection. Lancet Infect Dis, 17 (6): 636-644. [PMID:28363637] |