dBET1

製品コードS8296 バッチS829601

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₃₈H₃₇ClN₈O₇S

分子量

785.27

CAS No.

1799711-21-9

Solubility (25°C)*

体外

DMSO

100 mg/mL (127.34 mM)

Ethanol

39 mg/mL (49.66 mM)

Water

˂1 mg/mL

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。	5.000mg/ml (6.37mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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。	0.830mg/ml (1.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 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	dBET1は、IC50が20 nMのCRBNベースのBET分解剤であり、高い選択性を示します。7,429のタンパク質のうち、MYCとPIM1の発現、およびBRD2、BRD3、BRD4の発現のみがdBET1処理によって有意に下方制御されます。
in vitro	Treatment with dBET1 elicits a comparable, modest effect on MYC and PIM1 expression. Its treatment downregulates MYC and PIM1 transcription, suggestive of secondary transcriptional effects and transcription of BRD4 and BRD3 are unaffected, consistent with post-transcriptional effects. Transcription of BRD2 is affected by this compound and protein stability of the BRD2 gene product is influenced by it. This chemical induces a potent and superior inhibitory effect on MV4;11 cell proliferation at 24 hours (measured by ATP content, IC50 = 0.14 μM). Exposure of primary leukemic patient blasts to this compound elicits dose-proportionate depletion of BRD4 and induction of apoptosis. This compound-mediated targeted degradation of BET proteins robustly dampens pro-inflammatory responses in LPS-stimulated microglia, that is, depletion of BRD2 and BRD4 with it is associated with dramatically reduced LPS-induced COX-2 and iNOS protein levels and pro-inflammatory gene transcription of Nos2, Il-1β, Il-6, Tnfα, Ccl2, Ptgs2, and Mmp9.
in vivo	Administration of dBET1 attenuates tumor progression and decreases tumor weight assessed post-mortem in murine xenograft model of human MV4;11 leukemia cells. Pharmacokinetic studies of this compound (50 mg/kg IP) corroborate adequate drug exposure in vivo (Cmax = 392 nM, Tmax=0.5 hr, terminal t_1/2=6.69 hr, AUC_last=2109 hrng/ml, AUC_INF=295 hrng/ml). Two weeks of this chemical is well tolerated by mice without a meaningful effect on weight, white blood count, hematocrit or platelet count.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	SUM149 cells
	濃度	'0.1, 0.5, 1, 5, 10 μM
	反応時間	18 h
	実験の流れ	Immunoblot analysis
動物実験	動物モデル	Murine xenograft model of human MV4;11 leukemia cells (CD1 mice)
	投薬量	50 mg/kg daily
	投与方法	i.p.

参考

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937790/
https://pubmed.ncbi.nlm.nih.gov/29448097/

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：

BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 10.3892/etm.2023.12241]	PubMed: 37869639
BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 26(5):542]	PubMed: 37869639
Protein Ligand Interactions Using Surface Plasmon Resonance [ Methods Mol Biol, 2021, 2365:3-20]	PubMed: 34432236

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。