A pyrazine-2-carboxamide antimalarial that cures mice in one dose has entered phase 1
- A P. falciparum growth-inhibition screen identified a new pyrazine-2-carboxamide series for blood-stage malaria.
- Lead optimization improved anti-plasmodial potency and metabolic stability and reduced CYP2D6 inhibition risk, giving IWY357.
- A single dose was fully curative in a Pf-humanized SCID mouse model, resistance selection showed a high barrier, and the compound has progressed through GLP toxicology into phase 1.
💡 Points
A phenotypic hit taken all the way to the clinic with a single-dose cure in the humanized-mouse model is what the field has wanted since resistance to front-line agents began eroding. The CYP2D6 fix matters for combinations, which is where a short-course regimen would actually live. I would watch the human PK, since a single-dose claim lives or dies on exposure.