SCH00013
目录号 : GC32517
SCH00013是一个强心剂，主要通过增加肌纤维的Ca++的敏感性。
Cas No.:217963-18-3
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SCH00013 is a cardiotonic agent that primarily acts via an increase in myofibrillar Ca++ sensitivity, have a significant Ca(2+)sensitizing effect at pH 7.2 to 7.4.In vitro: SCH00013 at 10-4 M increased the systolic cell shortening by 52% above the base-line value in association with an insignificant increase in the systolic fluorescence ratio by 15% above the control. [1]In vivo: The positive inotropic effects of 10?4 M SCH00013 on the dog and rabbit were 38% and 29% of the maximal response to isoproterenol. [1] CH00013 elicited a positive inotropic effect at more than 0.3 and 1 mg/kg, i.v. in normal and heart failure dogs. [2] SCH00013 elicits a positive inotropic effect mainly through an increase in myofilament Ca2+ sensitivity without increasing the heart rate. [3]
[1]. Sugawara H et al. A novel cardiotonic agent SCH00013 acts as a Ca++ sensitizer with no chronotropic activity in mammalian cardiac muscle. J Pharmacol Exp Ther. 1998 Oct;287(1):214-22. [2]. Tadano N et al. SCH00013, a novel Ca(2+) sensitizer with positive inotropic and no chronotropic action in heart failure. J Pharmacol Sci. 2005 Jan;97(1):53-60. [3]. Endoh M et al. Pharmacology of SCH00013: a novel Ca2+ sensitizer. Cardiovasc Drug Rev. 2001 Winter;19(4):345-66.
| Cas No. | 217963-18-3 | SDF | |
| Canonical SMILES | N#CC1=CC=C(C(O)CN2CC=C(C(CC3)=NNC3=O)CC2)C=C1 | ||
| 分子式 | C18H20N4O2 | 分子量 | 324.38 |
| 溶解度 | Soluble in DMSO | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0828 mL | 15.414 mL | 30.828 mL |
| 5 mM | 0.6166 mL | 3.0828 mL | 6.1656 mL |
| 10 mM | 0.3083 mL | 1.5414 mL | 3.0828 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。
Pharmacology of SCH00013: a novel Ca2+ sensitizer
Cardiovasc Drug Rev 2001 Winter;19(4):345-66.PMID:11830752DOI:10.1111/j.1527-3466.2001.tb00075.x.
Cardiotonic agents that facilitate cardiac pump function by direct improvement of contractile dysfunction are indispensable for the treatment of hemodynamic disorders in acute myocardial failure and the aggravating phase of congestive heart failure. Cardiotonic agents currently available for the treatment of hemodynamic crisis in congestive heart failure are catecholamines, selective phosphodiesterase (PDE) III inhibitors and digitalis, all of which are Ca2+ mobilizers. Considering the number of serious adverse effects of these clinically available cardiotonic agents, development of agents that act via a novel mechanism of action may contribute to the progress of pharmacotherapy of congestive heart failure. Ca2+ sensitizers that act by increasing in myofilament Ca2+ sensitivity may be able to overcome the disadvantage of Ca2+ mobilizers. Ca2+ sensitizers do not increase activation energy, do not produce Ca2+ overload and may be effective even under pathophysiological states such as acidosis, myocardial stunning and heart failure. SCH00013 ((4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one)) is a novel Ca2+ sensitizer that elicits a moderate positive inotropic effect without significant alteration of Ca2+ transients. SCH00013 does not have a positive chronotropic effect and has a weak PDE III inhibitory action and class III antiarrhythmic action. SCH00013 prolonged the survival in a animal heart failure model with genetic cardiomyopathy. The oral bioavailability of SCH00013 is high and equivalent to that via intravenous administration. The unique pharmacological profiles of SCH00013 imply that this agent may be potentially beneficial for pharmacotherapy of contractile dysfunction in congestive heart failure.
SCH00013, a novel Ca(2+) sensitizer with positive inotropic and no chronotropic action in heart failure
J Pharmacol Sci 2005 Jan;97(1):53-60.PMID:15644593DOI:10.1254/jphs.fp0040654.
We investigated the effects of the agent SCH00013 on Ca(2+)-induced force generation in rabbit skinned cardiac muscle fibers and in vivo cardiac function in high-pacing-induced heart failure dogs. The Ca(2+)-induced force generation in skinned cardiac muscle fibers was determined at pH 6.2 - 7.4, and SCH00013 was found to have a significant Ca(2+) sensitizing effect at pH 7.2 to 7.4. There was no significant difference in the Ca(2+) sensitizing action between the enantiomers of SCH00013. The Ca(2+) sensitizing effect of SCH00013 was dependent on the sarcomere length, being significant only at a long sarcomere length. SCH00013 elicited a positive inotropic effect at more than 0.3 and 1 mg/kg, i.v. in normal and heart failure dogs, respectively, with no chronotropic action. These results strongly suggested that SCH00013 is a novel Ca(2+) sensitizer that elicits a positive inotropic and no chronotropic effect in heart failure, probably through enhancing the Frank-Starling mechanism.
Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 2nd communication: in vivo cardiovascular effects and bioavailability in dogs
Arzneimittelforschung 1999 May;49(5):407-11.PMID:10367102DOI:10.1055/s-0031-1300435.
In vivo cardiovascular effects and bioavailability of 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6- tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013), a novel cardiotonic agent, were investigated. In anesthetized dogs, intravenous administration of SCH00013 (0.3-10 mg/kg) increased maximum rate of rise in left ventricular pressure (LVdP/dtmax) in a dose-dependent manner with no change in heart rate (HR) and, at the dose of 3 mg/kg or higher, at which the increase in LVdP/dtmax reached the maximum, it decreased blood pressure. In conscious dogs, oral administration of SCH00013 (1-10 mg/kg) also increased LVdP/dtmax dose-dependently with no change in HR. The increase in the plasma concentration of orally administered SCH00013 (3 mg/kg) was parallel to the increase in LVdP/dtmax. The areas under the plasma concentration versus time curve (AUC0-24 h) after oral and intravenous administration of SCH00013 (3 mg/kg) were essentially identical (15.3 +/- 2.0 micrograms.h/ml and 16.5 +/- 2.1 micrograms.h/ml, respectively). These results suggest that oral bioavailability of SCH00013 is notably high. In conclusion, the positive inotropic effect of SCH00013 with neither elevation of HR nor excessive hypotension, as well as the high oral bioavailability of this compound, may provide a beneficial pharmacological treatment of the patients with congestive heart failure.
Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 3rd communication: stereoselectivity of the enantiomers in cardiovascular effects
Arzneimittelforschung 1999 May;49(5):412-9.PMID:10367103DOI:10.1055/s-0031-1300436.
The cardiovascular effects of the enantiomers, (+)-SCH00013 and (-)-SCH00013, of a novel cardiotonic agent 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]- 1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013) were investigated in vitro and in vivo. The enantiomers of SCH00013 elicited an equipotent positive inotropic effect in isolated guinea-pig papillary muscles. Both of the enantiomers had a modest negative chronotropic effect in isolated guinea-pig right atria and the difference in the chronotropic effects of the enantiomers was not significant. In anesthetized dogs, both enantiomers increased LVdP/dtmax without change in heart rate and slightly decreased blood pressure. These hemodynamic effects of the enantiomers were not significantly different from each other. (+)-SCH00013 and (-)-SCH00013 increased the extent of cell shortening in association with only a small increase in the Ca++ transients in indo-1-loaded rabbit cardiomyocytes, and both the increases in cell shortening and Ca++ transients were not significantly different between the enantiomers. Both isomers equally shifted the relationships between the increases in the cell shortening and Ca++ transients to the left and upward as compared with the relationships for the elevation of extracellular Ca++ concentration and isoproterenol, which indicates that the effectiveness of the Ca++ sensitizing effects of the enantiomers are almost equivalent. The enantiomers of SCH00013 showed equipotent inhibitory effect on the phosphodiesterase (PDE) III activity. The maximal extent and the potency of prolonging effect of the two enantiomers on the effective refractory period were also the same. Thus, the efficacy and potency of the effects on the cardiovascular parameters such as myofibrillar Ca++ sensitivity, PDE III activity and the effective refractory period for the both enantiomers of SCH00013 are equivalent, indicating that the cardiovascular effects of SCH00013 may be due to equal contribution of both enantiomers.
A novel cardiotonic agent SCH00013 acts as a Ca++ sensitizer with no chronotropic activity in mammalian cardiac muscle
J Pharmacol Exp Ther 1998 Oct;287(1):214-22.PMID:9765340doi
We investigated the inotropic effect of SCH00013 (4, 5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5, 6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one) on isolated dog and rabbit ventricular muscles and in indo-1 loaded rabbit ventricular cardiomyocytes. SCH00013 elicited a positive inotropic effect in a concentration-dependent manner (10(-6) to 10(-4) M) in both species in the presence of bupranolol. The positive inotropic effects of 10(-4) M SCH00013 on the dog and rabbit were 38% and 29% of the maximal response to isoproterenol. SCH00013 did not alter the rate of beating in isolated rabbit right atria. In indo-1 loaded rabbit ventricular cardiomyocytes, SCH00013 at 10(-4) M increased the systolic cell shortening by 52% above the base-line value in association with an insignificant increase in the systolic fluorescence ratio by 15% above the control. SCH00013 shifted the relationship between the Ca++ transients and cell shortening to the left as compared with that of elevation of [Ca++]o. In the dog and rabbit ventricular muscles, carbachol partially inhibited the positive inotropic effect of SCH00013. SCH00013 did not affect the positive inotropic effect of isoproterenol at 3 x 10(-6) M, but enhanced it at 3 x 10(-5) M. These results indicate that SCH00013 is a cardiotonic agent that primarily acts via an increase in myofibrillar Ca++ sensitivity with a moderate contribution of the cAMP-dependent mechanism at higher concentrations. SCH00013 has no chronotropic activity. The pharmacological profile of SCH00013 implies that the compound may be a promising cardiotonic agent for the treatment of congestive heart failure.