Nemtabrutinib (ARQ 531)

製品コードS8711 バッチS871101

印刷

化学情報

Synonyms

MK-1026

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₅H₂₃ClN₄O₄

分子量

478.93

CAS No.

2095393-15-8

Solubility (25°C)*

体外

DMSO

95 mg/mL (198.35 mM)

Ethanol

7 mg/mL (14.61 mM)

Water

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。	4.750mg/ml (9.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 95 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。	0.475mg/ml (0.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 9.5 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	Nemtabrutinib (ARQ 531, MK-1026) is an ATP-competitive tyrosine kinase inhibitor designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family kinases.
in vitro	Potently inhibiting BTK (IC50 = 0.85 nM), Nemtabrutinib (ARQ 531) exhibited a long residence time (51 min). It selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), this compound potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein^[2].
in vivo	Nemtabrutinib (ARQ 531) has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models^[1]. It crosses the blood, brain-barrier^[2]. In a single oral dose study of 10mg/kg in monkeys, the bioavailability of this compound is 72.4% with a Cmax of 9 μM and a half-life greater than 24 hours^[3].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	CLL cells
	濃度	0.1 μM, 1.0 μM, or 10.0 μM
	反応時間	72 h
	実験の流れ	--
動物実験	動物モデル	B6 mice engrafted with 1E7 CD5+/CD19+ TCL1 lymphocytes via tail vein injection
	投薬量	50 or 75 mg/kg
	投与方法	by oral gavage

参考

https://www.arqule.com/wp-content/uploads/ARQ531_EHA_2017.pdf
http://cancerres.aacrjournals.org/content/78/13_Supplement/1963.short
http://www.bloodjournal.org/content/128/22/3232?sso-checked=true

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：

BTK inhibition sensitizes Acute Lymphoblastic Leukemia to asparaginase by suppressing the Amino Acid Response pathway [ Blood, 2021, blood.2021011787]	PubMed: 34280258

BTK inhibition sensitizes Acute Lymphoblastic Leukemia to asparaginase by suppressing the Amino Acid Response pathway [ Blood, 2021, blood.2021011787]

PubMed: 34280258

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。