cipargamin + KLU156

cipargamin + KLU156 is an experimental antimalarial combination therapy currently in advanced clinical development. The combination consists of **cipargamin (KAE609)**, a spiroindolone that acts by inhibiting *Plasmodium falciparum* P-type ATPase 4 (PfATP4), disrupting ion homeostasis in the parasite, and **KLU156**, a fixed-dose formulation of **ganaplacide (KAF156)**, an imidazolopiperazine agent, combined with a solid dispersion formulation of lumefantrine (lumefantrine-SDF). - Cipargamin exhibits rapid blood-stage parasiticidal activity and transmission-blocking effects through inhibition of the Na^+^ efflux transporter PfATP4. - Ganaplacide (KAF156) shows potent activity against both hepatic and asexual/sexual blood stages and is proposed to act through disruption of protein folding and trafficking within the endoplasmic reticulum (ER), although its precise molecular mechanism is not fully elucidated. Lumefantrine inhibits heme detoxification in the parasite. - The combination is being developed principally for the treatment of uncomplicated *Plasmodium falciparum* malaria, including cases with resistance to artemisinin and partner drugs, and could serve as an alternative to current artemisinin-based combination therapies (ACTs), especially in areas of multidrug resistance. - The regimen is under investigation in children and adults in phase 2 and 3 studies.

Other names

ganaplacide + lumefantrine-SDFKAF156 + lumefantrine-SDFcipargamin + ganaplacide + lumefantrine-SDF