Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase

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Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase

Target not currently curated in GtoImmuPdb

Target has curated data in GtoMPdb

Target id: 2971

Nomenclature: Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase

Abbreviated Name: PfATP4

Family: Transporters (Plasmodium spp.)

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Plasmodium falciparum 3D7	-	1264		ATP4	non-SERCA-type Ca2+ -transporting P-ATPase

Previous and Unofficial Names
ATP4 \| Pf3D7_12_v3:527,829..533,965(-) \| P-type ATPase4 \| Plasmodium falciparum ATPase4 \| PFL0590c

Database Links
Alphafold	A0A143ZZK9 (Pf3D7)
PlasmoDB	PF3D7_1211900 (Pf3D7)
UniProtKB	A0A143ZZK9 (Pf3D7)

Ligand		Sp.	Assay description	Type	Action	Value	Parameter	Reference
PA21A092		PfTM90C2B Plasmodium falciparum TM90C2B P. falciparum TM90C2B (PfTM90C2B) is a clinical isolate, first described during a Phase 2 clinical trial to determine atovaquone efficacy in Thailand (PMID:8651372). A point mutation (Y268S) at the Q_o site of cytochrome b results in a 3,000-fold loss of atovaquone sensitivity. It is used as a screening tool for the development of new cytochrome b inhibitors. ✖	Parasite growth inhibition assay	-	-	7.9	pEC₅₀	9
⤷	pEC₅₀ 7.9 (EC₅₀ 1.3x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		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	pEC₅₀	9
⤷	pEC₅₀ 7.8 (EC₅₀ 1.4x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	7.7	pEC₅₀	9
⤷	pEC₅₀ 7.7 (EC₅₀ 1.8x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		PfFCR3 Plasmodium falciparum FCR3 P. falciparum strain FCR3 (PfFCR3) was originally isolated from a patient in The Gambia, West Africa in 1976. PfFCR3 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4). Differences in sensitivity of PfFCR3 clones to chloroquine have been reported, with the original isolate that was chloroquine sensitive rapidly acquiring resistance in culture (PMID: 7031656, PMID: 51801). ✖	Parasite growth inhibition assay	-	-	7.7	pEC₅₀	9
⤷	pEC₅₀ 7.7 (EC₅₀ 1.9x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1a [WO2021204952A1]		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	7.7	pEC₅₀	3
⤷	pEC₅₀ 7.7 (EC₅₀ 1.9x10^-8 M) SYBR Green assay [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
(+)-SJ733		PfDd2 Plasmodium falciparum Dd2 P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy. PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine. ✖	Parasite growth inhibition assay	-	-	7.7	pEC₅₀	4
⤷	pEC₅₀ 7.7 (EC₅₀ 2x10^-8 M) SYBR Green I assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		PfDd2 Plasmodium falciparum Dd2 P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy. PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine. ✖	Parasite growth inhibition assay	-	-	7.7	pEC₅₀	9
⤷	pEC₅₀ 7.7 (EC₅₀ 2.2x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
(+)-SJ733		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	7.5	pEC₅₀	4
⤷	pEC₅₀ 7.5 (EC₅₀ 3x10^-8 M) SYBR Green I assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		PfHB3 Plasmodium falciparum HB3 P. falciparum strain HB3 (PfHB3) was cloned from the Honduras I/CDC strain, originally isolated from a patient in Choluteca, Honduras, during an outbreak of urban malaria in January 1980. PfHB3 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be chloroquine sensitive. ✖	Parasite growth inhibition assay	-	-	7.5	pEC₅₀	9
⤷	pEC₅₀ 7.5 (EC₅₀ 3.2x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		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	-	-	7.4	pEC₅₀	9
⤷	pEC₅₀ 7.4 (EC₅₀ 3.8x10^-8 M) [³H]-hypoxanthine incorporation [9] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
(+)-SJ733		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	-	-	7.4	pEC₅₀	4
⤷	pEC₅₀ 7.4 (EC₅₀ 4x10^-8 M) SYBR Green I assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
PA21A092		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 dual gamete formation assay (DGFA)	-	-	7.1 – 7.4	pEC₅₀	9
⤷	pEC₅₀ 7.4 (EC₅₀ 3.9x10^-8 M) inhibition of gamete formation from mature Stage V male gametocytes [9] Lifecycle stages: Plasmodium sexual blood stage (gametocyte) pEC₅₀ 7.1 (EC₅₀ 7.4x10^-8 M) inhibition of gamete formation from mature Stage V female gametocytes [9] Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
(+)-SJ733		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	-	-	7.2	pEC₅₀	4
⤷	pEC₅₀ 7.2 (EC₅₀ 6x10^-8 M) SYBR Green I assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	9.3	pIC₅₀	5
⤷	pIC₅₀ 9.3 (IC₅₀ 5x10^-10 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	9.3	pIC₅₀	5
⤷	pIC₅₀ 9.3 (IC₅₀ 5x10^-10 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	9.2	pIC₅₀	5
⤷	pIC₅₀ 9.2 (IC₅₀ 6x10^-10 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	9.1	pIC₅₀	5
⤷	pIC₅₀ 9.1 (IC₅₀ 7x10^-10 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	9.1	pIC₅₀	5
⤷	pIC₅₀ 9.1 (IC₅₀ 9x10^-10 M) [³H]-hypoxanthine incorporation assay [5]
cipargamin		PfTM91C235 Plasmodium falciparum TM91C235 P. falciparum TM91C235 (PfTM91C235) is a clinical isolate from a patient in Thailand who failed mefloquine treatment twice. It can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, sulfadoxime, pyrimethamine and quinine. ✖	Parasite growth inhibition assay	-	-	9.1	pIC₅₀	5
⤷	pIC₅₀ 9.1 (IC₅₀ 9x10^-10 M) [³H]-hypoxanthine incorporation assay [5]
cipargamin		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	-	-	9.0	pIC₅₀	5
⤷	pIC₅₀ 9.0 (IC₅₀ 1x10^-9 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	8.9	pIC₅₀	5
⤷	pIC₅₀ 8.9 (IC₅₀ 1.2x10^-9 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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	-	-	8.9	pIC₅₀	5
⤷	pIC₅₀ 8.9 (IC₅₀ 1.4x10^-9 M) [³H]-hypoxanthine incorporation assay [5] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
GSK030		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	Parasite growth inhibition assay	-	-	7.3	pIC₅₀	1
⤷	pIC₅₀ 7.3 (IC₅₀ 5.2x10^-8 M) [³H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV897698		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	6.4	pIC₅₀	8
⤷	pIC₅₀ 6.4 (IC₅₀ 3.8x10^-7 M) SYBR Green I assay [8] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV1803022		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 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	-	-	6.3	pIC₅₀	7
⤷	pIC₅₀ 6.3 (IC₅₀ 4.6x10^-7 M) SYBR Green I assay [7] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cipargamin		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 early stage (I–II) gametocyte assay	-	-	-	-	10
⤷	Giemsa-stained blood film counts: dose-dependent, significant inhibition of stage II gametocyte development [10] Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
cipargamin		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 late stage (III–V) gametocyte assay	-	-	-	-	10
⤷	Giemsa-stained blood film counts: dose-dependent, inhibition of stage V gametocyte development [10] Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
cipargamin		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. ✖	Standard membrane feeding assay (SMFA)	-	-	-	-	10
⤷	Oocyst count: significantly reduced count observed with the addition of cipargamin when compared to control feeds [10] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
compound 1a [WO2021204952A1]		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. ✖	Standard membrane feeding assay (SMFA)	-	-	-	-	3
⤷	Relative oocyst intensities, determined using transgenic reporter strain P. falciparum NF54-HGL, show that compound 1a has transmission-blocking potential [3] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)

Malaria Pharmacology Comments
Mutations in PfATP4 have been shown to confer resistance by the Plasmodium parasite to the activity of a chemically diverse range of antimalarial drug candidates, including the spiroindolones, the dihydroisoquinolones and the aminopyrazoles [2,4-5]. Exposure of the parasite to these drug classes disrupts Na⁺ regulation [4,6], with the maintenance of a low cytosolic Na⁺ concentration essential for parasite survival during the intraerythrocytic stages of development. The exact interaction and mechanism by which these compounds lead to parasite death have not been fully elucidated, but host-mediated clearance of infected erythrocytes may be responsible for the rapid action of PfATP4 inhibitors [4].

Malaria Pharmacology Comments

Mutations in PfATP4 have been shown to confer resistance by the Plasmodium parasite to the activity of a chemically diverse range of antimalarial drug candidates, including the spiroindolones, the dihydroisoquinolones and the aminopyrazoles [2,4-5]. Exposure of the parasite to these drug classes disrupts Na⁺ regulation [4,6], with the maintenance of a low cytosolic Na⁺ concentration essential for parasite survival during the intraerythrocytic stages of development. The exact interaction and mechanism by which these compounds lead to parasite death have not been fully elucidated, but host-mediated clearance of infected erythrocytes may be responsible for the rapid action of PfATP4 inhibitors [4].

References

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1. Diaz-Hernandez B., Fernandez Velando E.P., Wilson D.M. (2016) Thiotriazole compound and its use in parasitic protozoal infections. Patent number: WO2016102431A1. Assignee: GlaxoSmithKline. Priority date: 22/12/2014. Publication date: 30/06/2016.

2. Flannery EL, McNamara CW, Kim SW, Kato TS, Li F, Teng CH, Gagaring K, Manary MJ, Barboa R, Meister S et al.. (2015) Mutations in the P-type cation-transporter ATPase 4, PfATP4, mediate resistance to both aminopyrazole and spiroindolone antimalarials. ACS Chem Biol, 10 (2): 413-20. [PMID:25322084]

3. Guy RK, Hammill JT, Floyd D, Burrows J, Brand S. (2021) New anti-malarial agents. Patent number: WO2021204952A1. Assignee: University of Kentucky Research Foundation, Medicines For Malaria Venture (MMV). Priority date: 09/04/2020. Publication date: 14/10/2021.

4. Jiménez-Díaz MB, Ebert D, Salinas Y, Pradhan A, Lehane AM, Myrand-Lapierre ME, O'Loughlin KG, Shackleford DM, Justino de Almeida M, Carrillo AK et al.. (2014) (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc Natl Acad Sci USA, 111 (50): E5455-62. [PMID:25453091]

5. Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B, Russell B, Seitz P, Plouffe DM, Dharia NV, Tan J et al.. (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science, 329 (5996): 1175-80. [PMID:20813948]

6. Spillman NJ, Allen RJ, McNamara CW, Yeung BK, Winzeler EA, Diagana TT, Kirk K. (2013) Na(+) regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe, 13 (2): 227-37. [PMID:23414762]

7. Tse EG, Aithani L, Anderson M, Cardoso-Silva J, Cincilla G, Conduit GJ, Galushka M, Guan D, Hallyburton I, Irwin BWJ et al.. (2021) An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials. J Med Chem, 64 (22): 16450-16463. [PMID:34748707]

8. Tse EG, Houston SD, Williams CM, Savage GP, Rendina LM, Hallyburton I, Anderson M, Sharma R, Walker GS, Obach RS et al.. (2020) Nonclassical Phenyl Bioisosteres as Effective Replacements in a Series of Novel Open-Source Antimalarials. J Med Chem, 63 (20): 11585-11601. [PMID:32678591]

9. Vaidya AB, Morrisey JM, Zhang Z, Das S, Daly TM, Otto TD, Spillman NJ, Wyvratt M, Siegl P, Marfurt J et al.. (2014) Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum. Nat Commun, 5: 5521. [PMID:25422853]

10. 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]

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Transporters (Plasmodium spp.): Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase. Last modified on 30/03/2022. Accessed on 15/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2971.