Omecamtiv mecarbil (CK-1827452)

製品コードS2623 バッチS262303

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H24FN5O3
分子量 401.43 CAS No. 873697-71-3
Solubility (25°C)* 体外 DMSO 80 mg/mL (199.28 mM)
Ethanol 14 mg/mL (34.87 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Omecamtiv mecarbil (CK-1827452) is a specific cardiac myosin activator and a clinical drug for left ventricular systolic heart failure. Phase 2.
in vitro In vitro, Omecamtiv mecarbil selectively activates cardiac myosin by increasing the myosin ATPase rate. [1] In isolated cardiac myocytes, Omecamtiv mecarbil results in increase of myocyte contractility and overcomes of the myosin inhibitor BDM without increasing the calcium transient or inhibiting the PDE pathway. [1]
in vivo Omecamtiv mecarbil significantly increases fractional shortening starting at 0.4 mM plasma concentrations in SD rats, sham animals and in rats with heart failure. [1] In conscious dogs with myocardial infarction (MI-sHF), Omecamtiv mecarbil leads to a significant increase in wall thickening (25%), stroke volume (44%), cardiac output (22%) and left ventricular (LV) systolic ejection time (26%). In addition, Omecamtiv mecarbil also results in the decreases of some hemodynamic parameters including heart rate, mean left atrial pressure, and LV end-diastolic pressure. In conscious dogs with left ventricular hypertrophy (LVH-sHF), Omecamtiv mecarbil leads to similar and not statistically different effects on hemodynamic parameters. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Biochemical assays
Cardiac S1 myosin and thin filament proteins (actin, troponin complex, and tropomyosin) are prepared from bovine heart or rabbit skeletal muscle. Smooth muscle myosin is prepared from chicken gizzard. ATPase assays are performed in a kinetic fashion using NADH coupled enzyme system at pCa2+ = 6.75. Rates are normalized to a DMSO control.
動物実験 動物モデル Sprague Dawley rats.
投薬量 ≤1.2 mg/kg/hour
投与方法 Administered via i.v.

カスタマーフィードバック

Data from [Data independently produced by University of Illinois at Chicago, 2014]

Data from [Data independently produced by , , J Physiol, 2018, 596(1):31-46]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The force of the myosin motor sets cooperativity in thin filament activation of skeletal muscles [ Commun Biol, 2022, 5(1):1266] PubMed: 36400920
Effects of omecamtiv mecarbil and mavacamten in isolated human atrium [ Naunyn Schmiedebergs Arch Pharmacol, 2022, 10.1007/s00210-022-02333-0] PubMed: 36399186
Myosin with hypertrophic cardiac mutation R712L has a decreased working stroke which is rescued by omecamtiv mecarbil [ Elife, 2021, 10e63691] PubMed: 33605878
Mechanistic analysis of actin-binding compounds that affect the kinetics of cardiac myosin-actin interaction [ J Biol Chem, 2021, S0021-9258(21)00245-3] PubMed: 33639160
Generative adversarial networks for construction of virtual populations of mechanistic models: simulations to study Omecamtiv Mecarbil action [ J Pharmacokinet Pharmacodyn, 2021, 10.1007/s10928-021-09787-4] PubMed: 34716531
Development and Application of NovelIn VitroAssays to Advance Drug Discovery for Arrhythmogenic Cardiomyopathy and Respiratory Syncytial Virus Infection [ ProQuest , 2021, 28718834] PubMed: none
Orthophosphate increases the efficiency of slow muscle-myosin isoform in the presence of omecamtiv mecarbil [ Nat Commun, 2020, 11(1):3405] PubMed: 32636378
Sarcomere integrated biosensor detects myofilament-activating ligands in real time during twitch contractions in live cardiac muscle [ J Mol Cell Cardiol, 2020, 147:49-61] PubMed: 32791214
Phosphorylation of Cardiac Myosin-Binding protein-C Contributes to Calcium Homeostasis [ J Biol Chem, 2020, jbc.RA120.13296] PubMed: 32554466
SarcTrack: An Adaptable Software Tool for Efficient Large-Scale Analysis of Sarcomere Function in hiPSC-Cardiomyocytes [Toepfer CN, et al. Circ Res, 2019, 10.1161/CIRCRESAHA.118.314505] PubMed: 30700234

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。