P218

Ligand id: 9740

Name: P218

Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
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

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
P218 has entered Phase 1 clinical trial for malaria. A first-in-human study to confirm the safety, tolerability and pharmacokinetics of P218 in healthy adult subjects has been completed (NCT02885506, last update March, 2018). A Phase 1b trial, to evaluate the safety, tolerability and chemoprotective activity of P218 in a P. falciparum sporozoite infection model has also been completed (NCT03707041, last update June, 2019).
Mechanism Of Action and Pharmacodynamic Effects
The P. falciparum enzyme, dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), catalyzes sequential reactions in the thymidylate cycle and is an important target of the antifolate class of antimalarial drugs. In contrast to the bifunctional protein of protozoan species, DHFR and TS are separate enzymes in higher eukaryotes and in bacteria. Resistance to the antifolate class of antimalarial drugs emerged soon after their clinical introduction and arisies from mutations in PfDHFR-TS [1].