Danicamtiv (MYK-491)

製品コードS9948 バッチS994801

印刷

化学情報

Synonyms

SAR 440181

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₁₆H₂₀F₃N₅O₄S

分子量

435.42

CAS No.

1970972-74-7

Solubility (25°C)*

体外

DMSO

87 mg/mL (199.8 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	4.350mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 87 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.725mg/ml (1.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 14.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	Danicamtiv (MYK-491, SAR 440181) is a novel cardiac myosin activator that enhances cardiomyocyte contraction.
in vitro	Danicamtiv (MYK-491) show high permeability and no efflux in a Caco-2 cell line, and its metabolism pathways in vitro included CYP-mediated amide-cleavage, N-demethylation, as well as isoxazole- and piperidine-ring-opening.<sup><a class="sref" href="#s_ref">[2]</a></sup>
in vivo	Selectively enhancing cardiac actomyosin activity, the molecular force‐generating unit of the sarcomere, Danicamtiv (MYK-491) prolongs contraction while preserving actin-myosin detachment, allowing relaxation, and without impacting Ca2+ homeostasis.^[1]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Caco-2/TC7 cell lines, male human hepatocytes
	濃度	1 µM, 10 µM
	反応時間	0, 2, 4, 6, 8, and 24 h
	実験の流れ	Incubations of plated human hepatocytes (1.4 million viable cells/mL, 0.2 mL, n = 2) with danicamtiv (MYK-491; 1 µM) are performed in a cell culture incubator (37 °C, 5% CO<sub>2</sub>, 95% humidity). Incubations are quenched with 200 µL of ACN containing 50 nM CBZ internal standard at incubation times 0, 2, 4, 6, 8, and 24 h. Supernatants are analysed by LC-MS/MS for the analysis of this compound from preclinical pharmacokinetic studies. Caco-2 cells are seeded on 96-well cell culture plates with PCF membrane filters and maintained for 21/25 days post-seeding with culture medium exchanged every 4th day. The bidirectional permeability (efflux) experiments are conducted on a TECAN automated liquid handling platform. It is examined at 1 and 10 μM, permeability controls are tested at 10 μM, and efflux controls are tested either at 2 μM or 1 μM in duplicate wells.
動物実験	動物モデル	male beagle dogs
	投薬量	2–3 mg/kg
	投与方法	p.o. , i. pl.

参考

https://pubmed.ncbi.nlm.nih.gov/32558989/
https://pubmed.ncbi.nlm.nih.gov/33078965/

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：

Danicamtiv reduces myosin's working stroke but enhances contraction by activating the thin filament [ bioRxiv, 2024, 2024.10.09.617269]	PubMed: 39416013
Effect of the Novel Myotrope Danicamtiv on Cross-Bridge Behavior in Human Myocardium [ J Am Heart Assoc, 2023, 12(20):e030682]	PubMed: 37804193

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。