Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Plasmodium falciparum 3D7	-	376		CYTB	cytochrome b

Previous and Unofficial Names

CYTB | Pf3D7_MIT_v3:3,492..4,622(+) | mal_mito_3

Database Links
ChEMBL Target	CHEMBL1777 (Pf)
PlasmoDB	PF3D7_MIT02300 (Pf3D7)
UniProtKB	Q02768 (Pf)

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Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference compound 11c [PMID: 30613327] 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. ✖ Inhibition 9.1 pIC50 3 ⤷ pIC50 9.1 (IC50 7.5x10-10 M) [3]

Whole Organism Assay Data Linked to This Target
Key to terms and symbols		Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference ELQ-300 Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖ Parasite liver stage assay - - 9.0 pEC50 4 ⤷ pEC50 9.0 (EC50 1.02x10-9 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms [4] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) compound 27 [PMID: 32945666] 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 - - 7.2 pEC50 2 ⤷ pEC50 7.2 (EC50 7x10-8 M) SYBR Green I assay [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 - - 10.0 pIC50 1 ⤷ pIC50 10.0 (IC50 1x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 - - 9.7 pIC50 1 ⤷ pIC50 9.7 (IC50 2x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 - - 9.5 pIC50 1 ⤷ pIC50 9.5 (IC50 3x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 1 ⤷ pIC50 9.3 (IC50 5x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 - - 9.2 pIC50 1 ⤷ pIC50 9.2 (IC50 6x10-10 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 - - 9.0 pIC50 1 ⤷ pIC50 9.0 (IC50 1.1x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) atovaquone 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 1 ⤷ pIC50 8.9 (IC50 1.4x10-9 M) [3H]-hypoxanthine incorporation [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 - - 8.6 – 8.7 pIC50 4 ⤷ pIC50 8.7 (IC50 1.8x10-9 M) SYBR green method, measured at 72h [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) pIC50 8.6 (IC50 2.27x10-9 M) [3H]-hypoxanthine incorporation [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 Qo 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 - - 8.6 – 8.8 pIC50 4 ⤷ pIC50 8.8 (IC50 1.7x10-9 M) SYBR green method, measured at 72h [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) pIC50 8.6 (IC50 2.84x10-9 M) [3H]-hypoxanthine incorporation [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 - - 8.6 pIC50 4 ⤷ pIC50 8.6 (IC50 2.5x10-9 M) SYBR green method, measured at 72h [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 - - 8.5 – 8.7 pIC50 4 ⤷ pIC50 8.7 (IC50 2.2x10-9 M) SYBR green method, measured at 72h [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) pIC50 8.5 (IC50 3.06x10-9 M) [3H]-hypoxanthine incorporation [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 - - 8.4 pIC50 4 ⤷ pIC50 8.4 (IC50 4.34x10-9 M) [3H]-hypoxanthine incorporation [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) compound 11c [PMID: 30613327] 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 - - 7.8 pIC50 3 ⤷ pIC50 7.8 (IC50 1.5x10-8 M) SYBR Green I method, measured at 48h [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) compound 11c [PMID: 30613327] 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 pIC50 3 ⤷ pIC50 7.5 (IC50 3.3x10-8 M) SYBR Green I method, measured at 48h [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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 (IV–V) gametocyte assay - - 7.1 pIC50 4 ⤷ pIC50 7.1 (IC50 7.19x10-8 M) High-content fluorescence-based image analysis of gametocyte viability throughout a period of 72 hours [4] Lifecycle stages: Plasmodium sexual blood stage (gametocyte) ELQ-300 Pc Plasmodium cynomolgi P. cynomolgi (Pc) is a malaria parasite that infects non-human primate species with the natural mammalian host being Asian Old World monkeys. Pc is used as a model for human P. vivax infection because these species are phylogenetically close and share a similar lifecycle, including the dormant liver form (hypnozoite). ✖ Parasite liver stage assay - - ~7.0 pIC50 4 ⤷ pIC50 ~7.0 (IC50 ~1x10-7 M) High-content fluorescence imaging to quantify the number of developing hepatic schizonts in primary rhesus hepatocytes infected with sporozoites from the M strain of P. cynomolgi [4] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) compound 27 [PMID: 32945666] Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖ Parasite liver stage assay - - 6.5 pIC50 2 ⤷ pIC50 6.5 (IC50 3x10-7 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms (EEF) [2] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) compound 11c [PMID: 30613327] 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 Qo 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 - - 6.3 pIC50 3 ⤷ pIC50 6.3 (IC50 5x10-7 M) SYBR Green I method, measured at 48h [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) ELQ-300 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–III) gametocyte assay - - - - 4 ⤷ Giemsa-stained blood film counts: treated gametocytes did not develop past stage III, even at 0.1 μM, the lowest dose tested [4] Lifecycle stages: Plasmodium sexual blood stage (gametocyte)

Malaria Pharmacology Comments

The cytochrome bc1 complex is the third component of the mitochondrial electron transport chain and is the target of several potent antimalarial compounds, including the naphthoquinone atovaquone and the 4(1H)-quinolone ELQ-300.