SJ-733

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SJ-733 (SJ000557733;SJ-557733) 是一种靶向 ATP4 的抗疟化合物，ATP4 是一种阳离子转运 ATP 酶，负责维持寄生虫细胞内较低的 Na(+) 水平。

SJ-733 (SJ000557733;SJ-557733) is an anti-malarial compound that targets ATP4, a cation-transporting ATPase responsible for maintaining low intracellular Na(+) levels in the parasite; displays high potency in vitro against all tested strains of P. falciparum with EC50 of 10-60 nM; kills parasites and the high fitness cost associated with resistance-conferring mutations appear to slow and suppress the selection of highly drug-resistant mutants in vivo; high oral bioavailabilityParasite Infection Phase 1 Clinical.

(+)-SJ733 binds to a single receptor site in P. falciparum-infected erythrocytes with equivalent affinity to its growth-inhibitory potency (kd=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.

Treatment of P. falciparum-infected NOD-scid IL2Rγnull 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 3D70087/N9 in vivo when administered as four sequential daily oral doses in the NOD-scid IL2Rγnull mouse model, with a 90% effective dose, (ED90 1.9 mg/kg) and exposure [area under the curve at ED90 (AUCED90), 1.5 μM?h] superior to artesunate (11.1 mg/kg; AUCED90 not determined), chloroquine (4.3 mg/kg; AUCED90 3.1 μM?h), and pyrimethamine (0.9 mg/kg; AUCED90 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.

+)-SJ733 | SJ000557733 | SJ-557733

Microbiology/Virology

Parasite

Parasite

Infection

Parasite Infection

1424799-20-1

468.412

C24H16F4N4O2

>98% (HPLC)

DMSO : 50 mg/mL 106.75 mM

O=C([C@@H](C1=C2C=CC=C1)[C@@H](C3=CC=CN=C3)N(CC(F)(F)F)C2=O)NC4=CC=C(F)C(C#N)=C4

(3S,4S)-N-(3-Cyano-4-fluorophenyl)-1-oxo-3-(3-pyridinyl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydro-4-isoquinolinecarboxamide

(-20℃)

With Ice Pack

≥ 2 years