Bioactivity Comments

The interaction table below provides data from an evaluation of the antimalarial (asexual blood stage) activity of artemisinin, using a panel of P. falciparum strains. Human proteins that are associated with the anticancer effects of artemisinin include tumor protein, translationally-controlled 1 (TPT1; P13693) [4] and microsomal prostaglandin E synthase 2 (mPGES2) [3].

Whole organism assay data
Key to terms and symbols	Click on species/strain names for details	Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference Unknown MOA PfV1/S Plasmodium falciparum V1/S P. falciparum strain V1/S (PfV1/S) is an in vitro culture-adapted clone of V1, that originated in Vietnam. PfV1/S can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and quinine. ✖ Parasite growth inhibition assay - - 9.2 pIC50 - 1 ⤷ pIC50 9.2 (IC50 6x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfD6 Plasmodium falciparum D6 P. falciparum strain D6 (PfD6) was collected in Sierra Leone. PfD6 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is generally considered drug sensitive with minor mefloquine resistance. ✖ Parasite growth inhibition assay - - 9.1 pIC50 - 1 ⤷ pIC50 9.1 (IC50 8x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA Pf7G8 Plasmodium falciparum 7G8 P. falciparum strain 7G8 (Pf7G8) was subcloned from the IMTM22 strain by limiting dilution. The original IMTM22 strain was isolated from a 12 year old male near Manaus, Brazil in 1980. Pf7G8 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4). This strain is a gametocyte producer and is reported to be chloroquine-sensitive and pyrimethamine-resistant. ✖ Parasite growth inhibition assay - - 8.5 pIC50 - 1 ⤷ pIC50 8.5 (IC50 3x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfK1 Plasmodium falciparum K1 P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979. PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain. ✖ Parasite growth inhibition assay - - 8.3 pIC50 - 1 ⤷ pIC50 8.3 (IC50 5.4x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖ Parasite growth inhibition assay - - 8.2 pIC50 - 1 ⤷ pIC50 8.2 (IC50 5.8x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfW2 Plasmodium falciparum W2 P. falciparum strain W2 (PfW2) was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy. PfW2 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and susceptible to mefloquine. ✖ Parasite growth inhibition assay - - 8.1 pIC50 - 1 ⤷ pIC50 8.1 (IC50 7.1x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfTM90C2A Plasmodium falciparum TM90C2A P. falciparum TM90C2A (PfTM90C2A) is a clinical isolate, first described during a Phase 2 clinical trial to determine atovaquone efficacy in Thailand (PMID:8651372). PfTM90C2A is sensitive to atovaquone. ✖ Parasite growth inhibition assay - - 7.8 pIC50 - 1 ⤷ pIC50 7.8 (IC50 1.51x10-8 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)

Targets where the ligand is described in the comment field
Target	Comment
zinc finger DHHC-type palmitoyltransferase 6	Catalyses protein S-palmitoylation of substrate proteins. ZDHHC6 substrates include calnexin (CANX), thioredoxin related transmembrane protein 1 (TMX1) [5], and the oncogenic NRAS GTPase [6]. The antimalarial drug artemisinin inhibits ZDHHC6-mediated palmitoylation of NRAS and calnexin [6]. Blocking NRAS palmitoylation with artemisinin disrupts its subcellular localisation and downstream proliferative signalling, and contributes towards the anticancer activity of artemisinin and its analogues [6].
mPGES2	Heme-free mPGES2 catalyses the isomerisation of prostaglandin H2 (PGE2) to prostaglandin E2 (PGE2) in the presence of glutathione (GSH); in contrast heme-bound mPGES2 catalyses the degradation of PGH2 to 12-hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA) [7,9-10]. In colon cancer cells artemisinin has been reported to bind reversibly to mPGES2 (occupying the PGH2 site), with the effect of blocking PGE2 biosynthesis and inhibiting cell proliferation [3].