P218   Click here for help

GtoPdb Ligand ID: 9740

Synonyms: MMV000147
PDB Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: The antifolate compound P218 is a potent and selective inhibitor of P. falciparum bifunctional dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) and was designed to overcome the emergence of parasite resistance to this class of antimalarial compound [7].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 133.58
Molecular weight 360.18
XLogP 1.72
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help
Canonical SMILES CCc1nc(N)nc(c1OCCCOc1ccccc1CCC(=O)O)N
Isomeric SMILES CCc1nc(N)nc(c1OCCCOc1ccccc1CCC(=O)O)N
InChI InChI=1S/C18H24N4O4/c1-2-13-16(17(19)22-18(20)21-13)26-11-5-10-25-14-7-4-3-6-12(14)8-9-15(23)24/h3-4,6-7H,2,5,8-11H2,1H3,(H,23,24)(H4,19,20,21,22)
InChI Key VDGXZSSDCDPCRF-UHFFFAOYSA-N
Guide to Malaria Pharmacology Comments
P218 was selected from a structure-informed drug discovery process to develop inhibitors of the clinically validated target P. falciparum bifunctional dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) [7].
The compound is example 8 from patent WO2009048957 [6].

Potential Target/Mechanism Of Action: P218 inhibits both wild-type and clinically relevant mutated forms of PfDHFR-TS.
Target Candidate Profiles
Profile Intended Use Target Stage Comment References
TCP-1 reduce parasite burden asexual blood stages 7
TCP-4 chemoprotection hepatic schizonts 4
TCP-5 transmission reduction gametocytes 3