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(+)-SJ733

CAS No. : 1424799-20-1

MCE 国际站：(+)-SJ733

产品活性：(+)-SJ733 是一种抗疟疾剂，也是一个 Na⁺-ATPase PfATP4 抑制剂。

研究领域：Membrane Transporter/Ion Channel  |  Anti-infection

作用靶点：Na+/K+ ATPase  |  Parasite

In Vitro: (+)-SJ733 binds to a single receptor site in P. falciparum-infected erythrocytes with equivalent affinity to its growth-inhibitory potency (k_d=50 nM). (+)-SJ733 has not exhibited either significant safety liabilities at any dose in extensive profiling in vitro or significant safety or tolerability liabilities in either single- or repeat-dose studies at any dose tested in any preclinical species (no observed adverse effect level and maximum tolerated dose >240 mg/kg from 7-d repeat dosing study in rat). Therefore, (+)-SJ733 is expected to have a safety margin of at least 43-fold.

In Vivo: Treatment of P. falciparum-infected NOD-scid IL2Rγ^null mice with (+)-SJ733 causes rapid clearance of parasites, which are 80% depleted within the first 24 h and undetectable by 48 h. (+)-SJ733 is highly potent and efficacious against P. falciparum 3D7^0087/N9 in vivo when administered as four sequential daily oral doses in the NOD-scid IL2Rγ^null mouse model, with a 90% effective dose, (ED₉₀ 1.9 mg/kg) and exposure [area under the curve at ED₉₀ (AUC_ED90), 1.5 μM⋅h] superior to artesunate (11.1 mg/kg; AUC_ED90 not determined), chloroquine (4.3 mg/kg; AUC_ED90 3.1 μM⋅h), and pyrimethamine (0.9 mg/kg; AUC_ED90 5. μM⋅h) in the same model. When treated with the ED₉₀ dose, (+)-SJ733 concentrations in blood remain above the average in vitro EC₉₀ for 6 to 10 h after each dose.

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