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(+)-SJ733

Catalog No. T17313 CAS 1424799-20-1

Synonyms: SJ000557733

(+)-SJ733 (SJ000557733) is a potent Na+-ATPase PfATP4 inhibitor with antimalarial activity for the study of malaria.

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(+)-SJ733, CAS 1424799-20-1

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Purity: 99.21%

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Description	(+)-SJ733 (SJ000557733) is a potent Na+-ATPase PfATP4 inhibitor with antimalarial activity for the study of malaria.
Targets&IC50	single receptor site:50 nM (Kd)
In vitro	(+)-SJ733 has not exhibited any significant safety risks at any dose in extensive in vitro profiling, and in any study, there have been no notable safety or tolerability issues (no observed adverse effect level and maximum tolerated dose >240 mg/kg from a 7-day repeat dosing study in rats). Therefore, it is anticipated that (+)-SJ733 has a safety margin of at least 43-fold.[1].
In vivo	(+)-SJ733 is an efficacious and safe orally active drug candidate. (+)-SJ733 is efficacious against P. falciparum 3D70087/N9 in the nonobese diabetic Scid interleukin-2 receptor γ chain null (NSG) mouse model with the (+)-enantiomer exhibiting excellent potency (1.9 mg/kg); similar to pyrimethamine (ED90 0.9 mg/kg) and superior to chloroquine (ED90 4.3 mg/kg) in this model. (+)-SJ733 achieves this efficacy from exposure (AUCED90 1.5 µM⋅h) similar to that of chloroquine (AUCED90 3.1 µM⋅h) and superior to that of pyrimethamine (AUCED90 5.2 µM⋅h) in the same model.(+)-SJ733 exhibits excellent exposure after oral administration in mouse, rat, and dog. In rodents, (+)-SJ733 reaches peak plasma concentrations of ∼5 µM within 1 h after 20–25 mg/kg doses and >20 µM in dogs following a 30 mg/kg oral dose.(+)-SJ733 exhibits no significant toxicology at doses up to 200 mg/kg in rats with an exposure (AUC) ∼43-fold higher than that required to produce the maximum parasitological response (fastest rate of killing) and 220-fold that required to produce the ED90 in the mouse, indicating the potential for an excellent therapeutic ratio[1].

Synonyms	SJ000557733
Molecular Weight	468.4
Formula	C24H16F4N4O2
CAS No.	1424799-20-1

Storage

store at low temperature

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 30 mg/mL (64.05 mM), Sonication is recommended.

References and Literature

1. Jimenez-Diaz MB, et al. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5455-62.

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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

(+)-SJ733 1424799-20-1 Membrane transporter/Ion channel Microbiology/Virology ATPase Parasite SJ000557733 SJ-733 (+)SJ733 SJ733 SJ 000557733 (+)-SJ-733 SJ 733 (+) SJ733 SJ-000557733 inhibitor inhibit

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