BML-277 (Chk2 Inhibitor II)

製品コードS8632 バッチS863201

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₀H₁₄ClN₃O₂

分子量

363.80

CAS No.

516480-79-8

Solubility (25°C)*

体外

DMSO

72 mg/mL (197.91 mM)

Ethanol

21 mg/mL (57.72 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。	3.600mg/ml (9.90mM)	Taking the 1 mL working solution as an example, add 50 μL of 72 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。	3.600mg/ml (9.90mM)	Taking the 1 mL working solution as an example, add 50 μL of 72 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	BML-277 (Chk2 Inhibitor II) は、IC50が15 nMのChk2のATP競合阻害剤です。Chk1およびCdk1/Bキナーゼと比較して、Chk2セリン/スレオニンキナーゼに対して1000倍以上の選択性を示します。Chk2 Inhibitor II (BML-277) は、電離放射線によるアポトーシスからヒトCD4(+)およびCD8(+) T細胞を用量依存的に保護します。
in vitro	BML-277 (Chk2 Inhibitor II) shows 1,000-fold greater selectivity for the CHK2 serine/threonine kinase than for the Cdk1/B and CK1 kinases and was first discovered to be a potent, selective small molecule showing radioprotection towards human T cells. Different doses of this compound specifically inhibit CHK2 phosphorylation at Thr68 at different time course, but not CHK1 phosphorylation. Treatment with combination of it and ERK inhibitor results in substantially more apoptosis compared with treatment of either drug alone.
in vivo	SUDHL6 DLBCL xenografts mice treated every other day intraperitoneally with either vehicle, ERK inhibitor (5 mg kg−1), BML-277 (Chk2 Inhibitor II) (1 mg kg−1), or both ERK inhibitor and this compound for 20 days show no lethal toxicity, significant weight loss or any gross abnormalities. Both 5 mg/kg ERK inhibitor and 1 mg/kg of it modestly inhibit tumour growth but combined treatment with ERK inhibitor and BML-277 results in a statistically significant suppression of tumour growth.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	human DLBCLs cells
	濃度	5 μM
	反応時間	48 h
	実験の流れ	Single-cell suspensions are obtained from lymph node biopsies of patients diagnosed with DLBCL and are treated with DMSO, ERK inhibitor and BML-277 (Chk2 Inhibitor II) alone or in combination for 48 h after which the percentage of apoptotic cells is determined by Annexin V analysis.
動物実験	動物モデル	SUDHL6 DLBCL xenografts (SCID mice)
	投薬量	1 mg/kg
	投与方法	i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/15771432/
https://pubmed.ncbi.nlm.nih.gov/21772273/

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：

Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer [ BMC Cancer, 2025, 25(1):1520]	PubMed: 41053754
DNA damage response pathway regulates Nrf2 in response to oxidative stress [ Sci Adv, 2025, 11(30):eadu9555]	PubMed: 40712037
CEP-1347 Boosts Chk2-Mediated p53 Activation by Ionizing Radiation to Inhibit the Growth of Malignant Brain Tumor Cells [ Int J Mol Sci, 2024, 25(17)9473]	PubMed: 39273420
Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia [ bioRxiv, 2024, 2024.06.24.600514]	PubMed: 38979390
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088]	PubMed: 37773176
Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response [ iScience, 2023, 26(7):107090]	PubMed: 37416470
Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death via Phosphorylation of p53 Regulated by ER Stress in Hepatocellular Carcinoma [ Cancers (Basel), 2023, 15(15)3987]	PubMed: 37568803
Precision Combination Therapies Based on Recurrent Oncogenic Coalterations [ Cancer Discov, 2022, 12(6):1542-1559]	PubMed: 35412613
ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance [ Cancer Res, 2022, 82(24):4571-4585.]	PubMed: 36353752
Wwox Binding to the Murine Brca1-BRCT Domain Regulates Timing of Brip1 and CtIP Phospho-Protein Interactions with This Domain at DNA Double-Strand Breaks, and Repair Pathway Choice [ Int J Mol Sci, 2022, 23(7)3729]	PubMed: 35409089

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。