Top ▲

Plasmodium sexual blood stage (gametocyte)

Stage ID:4
Name:Plasmodium sexual blood stage (gametocyte)
Associated with:2 targets
4 ligands
Description
The lifecycle stage during which a small percentage of merozoites commit to a cycle of sexual reproduction and differentiate into male or female gametocytes. It is this form of the parasite that is ingested in the vector's blood meal, leading to transmission back to the mosquito from the human host. The sexual blood stage can be further subdivided into stages I-V within the human host, with mature stage V gametocytes infective to the mosquito.

Blocking development of the parasite during this stage prevents transmission from human to mosquito.

Interactions

Interactions
Key to terms and symbols Click column headers to sort
Target Ligand Sp. Action Affinity Parameter Reference
Plasmodium falciparum ATPase4 cipargamin PfNF54 - - - 4
Giemsa-stained blood film counts: dose-dependent, significant inhibition of stage II gametocyte development [4]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite early stage (I–II) gametocyte assay
Giemsa-stained blood film counts: dose-dependent, inhibition of stage V gametocyte development [4]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite late stage (III–V) gametocyte assay
Plasmodium falciparum phosphatidylinositol 4-kinase MMV048 PfNF54 - 6.6 – 6.8 pIC50 3
pIC50 6.8 (IC50 1.4x10-7 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite gametocyte viability assay
pIC50 6.7 (IC50 2.14x10-7 M) Parasite early stage (I-III) gametocyte assay using luciferase reporter line [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite gametocyte viability assay
pIC50 6.6 (IC50 2.85x10-7 M) Parasite late stage (IV-V) gametocyte assay: parasitic lactate dehydrogenase (pLDH) assay [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite gametocyte viability assay
Plasmodium falciparum phosphatidylinositol 4-kinase UCT943 Pf - 6.9 – 7.2 pIC50 1
pIC50 7.2 (IC50 6.6x10-8 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite gametocyte viability assay
pIC50 6.9 (IC50 1.34x10-7 M) Parasite early stage (I-III) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite gametocyte viability assay
Unknown MOA ACT-451840 PfNF54 - 8.2 pIC50 2
pIC50 8.2 (IC50 5.89x10-9 M) male gamete formation from the gametocyte stage [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Description: Parasite dual gamete formation assay (DGFA)
Conditions: ACT-451840 had no effect on the functional viability of female gametocytes up to a concentration of 20 μM.

References

Show »

1. Brunschwig C, Lawrence N, Taylor D, Abay E, Njoroge M, Basarab GS, Le Manach C, Paquet T, Cabrera DG, Nchinda AT et al.. (2018) UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria. Antimicrob. Agents Chemother., 62 (9). [PMID:29941635]

2. Le Bihan A, de Kanter R, Angulo-Barturen I, Binkert C, Boss C, Brun R, Brunner R, Buchmann S, Burrows J, Dechering KJ et al.. (2016) Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. PLoS Med., 13 (10): e1002138. [PMID:27701420]

3. Paquet T, Le Manach C, Cabrera DG, Younis Y, Henrich PP, Abraham TS, Lee MCS, Basak R, Ghidelli-Disse S, Lafuente-Monasterio MJ et al.. (2017) Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med, 9 (387). [PMID:28446690]

4. van Pelt-Koops JC, Pett HE, Graumans W, van der Vegte-Bolmer M, van Gemert GJ, Rottmann M, Yeung BK, Diagana TT, Sauerwein RW. (2012) The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector. Antimicrob. Agents Chemother., 56 (7): 3544-8. [PMID:22508309]