Aims, Concerns and Current Interest in Series 4

Notable Points about The Series

1. • Compounds in this series have been identified down to 16 nM potency.
2. • Seems to have good ''in vitro'' HLM and hHEP stability: CL_int < 8.1 is compatible with 10 nM potency.
3. • RLM remains stubbornly high, particularly for the more potent analogues translating to short half-lives in rat PK. It's possible that rat metabolism may not be a good model for human metabolism for this series.
4. • Series appears to have little polypharmacology or cytotoxicity.
5. • There is strong correlation between activity ''vs.'' Pfal and activity in Kiaran Kirk’s ion regulation assay, implying the mechanism of action is inhibition of PfATP4.