| Chemical Properties | Back Directory | [Boiling point ]
784.8±70.0 °C(Predicted) | [density ]
1.42±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
10.41±0.70(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Purfalcamine is an orally active, selective Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) inhibitor with an IC50 of 17 nM and an EC50 of 230 nM. Purfalcamine has antimalarial activity and causes malaria parasites developmental arrest at the schizont stage[1][2]. | [Biological Activity]
Purfalcamine is an orally active and selective inhibitor of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) with IC50 of 17 nM and EC50 of 230 nM. It has antimalarial activity and can cause developmental arrest in the schizont stage of Plasmodium. | [in vitro]
Purfalcamine has low activity against Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3).
Purfalcamine (225, 450 nM) has no effect on the parasitemia in the first 32 hours. After about 40 hours, parasite level remains stable and then begins dropping.
Purfalcamine inhibits proliferation with EC 50 s of 171-259 nM for P. falciparum strains (3D7, Dd2, FCB, HB3 and W2), which indicate effectiveness against drug-resistant parasites.
Given that the EC 50 value for P. falciparum (3D7) is 230 nM, Purfalcamine shows a therapeutic window ranging from 23-fold to 36-fold (EC 50 s for CHO=12.33 μM, HEp2=7.235 μM, HeLa=7.029 μM and Huh7 =5.476 μM).
| [in vivo]
Purfalcamine (10 mg/kg; oral gavage; BID; for 6 days) demonstrates a delay in the onset of parasitemia in treated mice.
Purfalcamine (20 mg/kg; orally gavage) exhibits a C max of 2.6 μM with a half-life of 3.1 hours.
| Animal Model: | Male BALB/c mice, 7 weeks of age with the malaria parasite | | Dosage: | 10 mg/kg | | Administration: | Oral gavage; BID; for 6 days | | Result: | Demonstrated a delay in the onset of parasitemia in treated mice when compared with control mice. | | Animal Model: | Five- to six-week-ol d male Balb/c mice (22-25 g) | | Dosage: | 20 mg/kg (Pharmacokinetic Analysis) | | Administration: | Orally gavage | | Result: | Exhibited a maximum plasma exposure (C max ) of 2.6 μM with a half-life of 3.1 hours. | | [IC 50]
Plasmodium; Toxoplasma | [storage]
Store at -20°C | [References]
[1] Nobutaka Kato, et al. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol. 2008 Jun;4(6):347-56. DOI:10.1038/nchembio.87
[2] Rajshekhar Y Gaji, et al. Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Antimicrob Agents Chemother. 2014 May;58(5):2598-607. DOI:10.1128/AAC.02261-13 |
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MedChemExpress
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