(+)-SJ733 (SJ000557733)
(Synonyms: SJ000557733) 目录号 : GC32130
(+)-SJ733 (SJ000557733) 是一种抗疟疾药物，还可以抑制 Na+-ATPase PfATP4。
Cas No.:1424799-20-1
Sample solution is provided at 25 µL, 10mM.
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(+)-SJ733 is a clinical candidate for malaria which can also inhibit Na+-ATPase PfATP4.
(+)-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[1].
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[1].
[1]. Jiménez-Díaz 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.
Cell experiment: | 10 mL of asynchronous culture suspensions (2% hematocrit), at different parasite densities (104, 105, 106, 107, and 108 parasites), are added to each well of a 6-well plate. (+)-SJ733 is added to each well to make a final compound concentration of 1.8 μM, corresponding to 30×EC50 of the compound. Three wells are used for each parasite density. Plates are incubated at 37° C under an atmosphere of 90% N2, 5% O2, 5% CO2 for 90 days under constant drug pressure. The media of each well is replaced 3 times a week with freshly made media containing a compound concentration of 30×EC50. In addition, each well is split (1:2) once a week. Parasite outgrowth is monitored 3 times a week by transferring quadruplicate 40 μL aliquots from each well into a 384-well assay plate and determining parasitemia by a previously described method[1]. |
Animal experiment: | The pharmacokinetics of (+)-SJ733 are studied in overnight-fasted male Sprague Dawley rats weighing 267 to 291 g predose. Rats have access to water ad libitum throughout the pre- and post-dose sampling period, and access to food is reinstated 4 h post-dose. (+)-SJ733 is administered intravenously as a 10 min constant rate infusion (1.0 mL per rat, n=3 rats) and orally by gavage (10 mL/kg, n=3 rats). The IV formulation consists of pH 7.4 isotonic phosphate buffered saline containing 1% (w/v) hydroxypropyl-β-cyclodextrin, 10% (v/v) ethanol, 10% (v/v) propylene glycol and 40% (v/v) PEG400 whereas the oral formulation is an aqueous suspension in 0.5% (w/v) hydroxypropyl methylcellulose, 0.5% (v/v) benzyl alcohol and 0.4% (v/v) Tween80. Aliquots of the formulations are retained for analysis of the actual dose administered. Samples of arterial blood and total urine are collected at various time points up to 24 h post-dose[1]. |
References: [1]. Jiménez-Díaz 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. | |
| Cas No. | 1424799-20-1 | SDF | |
| 别名 | SJ000557733 | ||
| Canonical SMILES | 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 | ||
| 分子式 | C24H16F4N4O2 | 分子量 | 468.4 |
| 溶解度 | DMSO : 50 mg/mL (106.75 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1349 mL | 10.6746 mL | 21.3493 mL |
| 5 mM | 0.427 mL | 2.1349 mL | 4.2699 mL |
| 10 mM | 0.2135 mL | 1.0675 mL | 2.1349 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet