Istaroxime hydrochloride
(Synonyms: ISTAROXIME盐酸盐,PST-2744 (hydrochloride);PST 2744 (hydrochloride);PST2744 (hydrochloride)) 目录号 : GC17786
Istaroxime hydrochloride 是 Na+/K+-ATPase 抑制剂 (IC50=0.11 μM) 和肌质/内质网钙 ATPase 2 (SERCA 2) 激活剂。
Cas No.:374559-48-5
Sample solution is provided at 25 µL, 10mM.
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Istaroxime hydrochloride(PST2744) is a novel inhibitor of Na+/K+-ATPase with IC50 value of 0.43±0.15μM [1].
In vitro studies show that Istaroxime can inhibit the activity of Na+/K+-ATPase from dog kidney without significant interaction with other several receptors. It demonstrates the selectivity of Istaroxime. Ex vivo studies show the inotropic effect can be achieved up to 60% for Istaroxime. Istaroxime can also increase the force of contraction of guinea pig paced left atria in the range 0.3 to 30μM. In vivo assays prove Istaroxime is consistently safer than digoxin [1].
Istaroxime is a steroidal drug unrelated to cardiac glycosides that improves cellular calcium cycling. The inhibition of Na+/K+-ATPase induces cytosolic calcium accumulation during systole (inotropism). Clinical studies has been done with istaroxime in phase II. Istaroxime could be a promising alternative for patients with acute heart failure syndrome for whom the therapeutic options are currently limited [2].
References:
[1] R. Micheletti, G. G. Mattera, M. Rocchetti, A. Schiavone, M. F. Loi, A. Zaza, R. J. P. Gagnol, S. De Munari, P. Melloni, P. Carminati, G. Bianchi, and P. Ferrari. Pharmacological profile of the novel inotropic agent (e,z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744). The journal of pharmacology and experimental therapeutics. 2002, 303 (2): 592-600.
[2] Suruchi Aditya, Aditya Rattan. Istaroxime: A rising star in acute heart failure. Journal of Pharmacology and Pharmacotherapeutics. 2012, 3(4): 353-355.
| Cell experiment: [1] | |
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Cell lines |
Guinea pig ventricular myocytes |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
4 μM, 0.5 s |
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Applications |
Resting Ca2+ was similarly increased by istaroxime (from 61.3 to 92.4 nM). Istaroxime increased [Ca]SR-tot by 47%. Istaroxime increased the amount of Ca2+ extruded by the Na+/Ca2+ exchanger (CaNCX) during caffeine-induced transients (+130). Istaroxime shortened the time elapsing between the start of the caffeine pulse and SR Ca2+ release. |
| Animal experiment: [2] | |
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Animal models |
Bio TO.2 hamsters and Bio F1B hamsters |
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Dosage form |
Oral administration, 30 mg/5 mL/kg/day |
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Applications |
Heart function of istaroxime-treated hamsters was comparable to that of healthy animals, and had a significantly higher LVSP and both positive and negative dP/dT when compared with that of vehicle-treated animals. Coronary flow rate in hearts isolated from istaroxime-treated hamsters was higher than that from vehicle-treated Bio TO.2 animals. Besides that, Bio TO.2 hamsters treated with istaroxime had both time and frequency domain indexes of HRV, i.e. standard deviation of R-R intervals, TP, LF and HF, augmented with respect to vehicle-treated animals. Moreover , the LF/HF ratio of istaroxime-treated animals was similar to that observed in Bio F1B hamsters. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Rocchetti M, Besana A, Mostacciuolo G, et al. Modulation of sarcoplasmic reticulum function by Na+/K+ pump inhibitors with different toxicity: digoxin and PST2744 [(E, Z)-3-((2-aminoethoxy) imino) androstane-6, 17-dione hydrochloride]. Journal of Pharmacology and Experimental Therapeutics, 2005, 313(1): 207-215. [2] Giudice P L, Mattera G G, Gagnol J P, et al. Chronic istaroxime improves cardiac function and heart rate variability in cardiomyopathic hamsters. Cardiovascular drugs and therapy, 2011, 25(2): 133-138. |
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| Cas No. | 374559-48-5 | SDF | |
| 别名 | ISTAROXIME盐酸盐,PST-2744 (hydrochloride);PST 2744 (hydrochloride);PST2744 (hydrochloride) | ||
| 化学名 | (5S,8R,9S,10R,13S,14S)-3-(2-aminoethoxyimino)-10,13-dimethyl-1,2,4,5,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-6,17-dione;hydrochloride | ||
| Canonical SMILES | CC12CCC(=NOCCN)CC1C(=O)CC3C2CCC4(C3CCC4=O)C.Cl | ||
| 分子式 | C21H33ClN2O3 | 分子量 | 396.95 |
| 溶解度 | DMSO : ≥ 45 mg/mL (113.36 mM); H2O : 25 mg/mL (62.98 mM; Need ultrasonic) | 储存条件 | Store at 2-8°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 | 2.5192 mL | 12.596 mL | 25.1921 mL |
| 5 mM | 0.5038 mL | 2.5192 mL | 5.0384 mL |
| 10 mM | 0.2519 mL | 1.2596 mL | 2.5192 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