dBET6

製品コードS8762 バッチS876203

印刷

化学情報

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

C42H45ClN8O7S
分子量 841.37 CAS No. 1950634-92-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (118.85 mM)
Ethanol 33 mg/mL (39.22 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml 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 make it clear; 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. 
* <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 dBET6 is a highly cell-permeable PROTAC degrader of BET bromodomains with an IC50 of 14 nM for BRD4 binding. dBET6 also induces c-MYC downregulation and apoptosis.
in vitro

dBET6 is a highly cell-permeable degrader of BET bromodomains. It is potent in most cancer cell lines. dBET6 features highly increased cellular potency with evident degradation in the sub-nanomolar range. Treatment with 100 nM dBET6 leads to degradation of BRD4 after 1 hr, prompting subsequent downregulation of c-MYC and induction of apoptosis. dBET6 disrupts global productive transcription elongation. dBET6 treatment leads to a widespread decrease in steady-state mRNA levels, but observed an incommensurate impact on expression of members of the core regulatory circuitry of leukemogenic transcription factors. The collapse of the core transcriptional machinery prompted by BET degradation precedes a robust apoptotic response, of apparent translational significance[1].
in vivo

dBET6 is well tolerated. Upon dBET6 treatment, a significant reduction of leukemic burden is observed in a disseminated mouse model of T-ALL. Moreover, mice treated with dBET6 (7.5 mg/kg BID) exhibits a significant survival benefit compared to mice treated with vehicle control or JQ1 (20 mg/kg QD)[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MOLT4 cells deficient in CRBN expression
濃度 0.05, 0.1, 0.5, 1 μM
反応時間 3 hr
実験の流れ

MOLT4 cells deficient in CRBN expression are treated with various concentrations of either dBET1 or dBET6 for 3 hr. Cells are collected by centrifugation, washed once with PBS and transferred into PCR tubes, spun down and incubated at 47.5°C for 3 min. After a subsequent incubation for 3 min on 25°C, cells are lysed by addition of 30 µL lysis buffer and three repeated freeze-thaw cycles using liquid nitrogen.
動物実験 動物モデル Male CD-1 mice
投薬量 10 mg/kg
投与方法 i.p.

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：

Cell-type-specific tumour sensitivity identified with a bromodomain targeting PROTAC in adenoid cystic carcinoma [ J Pathol, 2024, 262(1):37-49] PubMed: 37792636
Increased expression of BRD4 isoforms long (BRD4-L) and short (BRD4-S) promotes chemotherapy resistance in high-grade serous ovarian carcinoma [ Genes Cancer, 2023, 10.18632/genesandcancer.233] PubMed: 37705995
Increased expression of BRD4 isoforms long (BRD4-L) and short (BRD4-S) promotes chemotherapy resistance in high-grade serous ovarian carcinoma [ Genes Cancer, 2023, 14:56-76] PubMed: 37705995
BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2 [ Nat Cell Biol, 2022, 24(1):24-34] PubMed: 35027731
Structure-guided discovery of novel potent and efficacious proteolysis targeting chimera (PROTAC) degrader of BRD4 [ Bioorg Chem, 2021, 115:105238] PubMed: 34390970
Epigenomic landscape and 3D genome structure in pediatric high-grade glioma [ Sci Adv, 2021, 7(23)eabg4126] PubMed: 34078608
BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2 [ bioRxiv, 2021, 2021.01.19.427194] PubMed: 33501440
Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2 [ bioRxiv, 2021, 2021.11.14.468537] PubMed: 34816261
Kinetic Detection of E3:PROTAC:Target Ternary Complexes Using NanoBRET Technology in Live Cells [ Methods Mol Biol, 2021, 2365:151-171] PubMed: 34432243
ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer [ Genome Med, 2020, 12(1):63] PubMed: 32669118

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。

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