Pelabresib (CPI-0610)

製品コードS7853 バッチS785302

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H16ClN3O2
分子量 365.81 CAS No. 1380087-89-7
Solubility (25°C)* 体外 DMSO 73 mg/mL (199.55 mM)
Ethanol 15 mg/mL (41.0 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
4.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 80 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. 
* <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 Pelabresib (CPI-0610) is a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor with an IC50 of 39 nM for BRD4-BD1 in TR-FRET assay and currently undergoing human clinical trials for hematological malignancies. CPI-0610 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.
in vitro

CPI-0610 inhibits MM(multiple myeloma) cell growth in the presence of cytokines and when co-cultured with bone marrow stromal cells. CPI-0610 induces apoptosis and G1 cell cycle arrest associated with MYC downregulation. However, protein levels of BCL2, NF-κB and MCL1 remain unchanged in MM cells upon BET inhibition. CPI-0610 suppresses Ikaros and IRF4 expression at the levels of both transcription and protein in MM cells[2].
in vivo

In a mouse xenograft model using MV-4-11 acute myeloid leukemia cells, MYC mRNA levels of CPI-0610-treated mice were substantially reduced at 4 h compared to the vehicle control and recovered toward the control level at the later time points, which corresponded with decreasing free concentrations of compound in plasma. BET bromodomain inhibition by CPI-01610 resulted in substantial suppression of tumor growth over the time period examined (41%, 80%, and 74% tumor growth inhibition, respectively), without any significant body weight loss in the animals. On the basis of an acceptable toxicity profile in rat and dog, A common set of toxicities was observed in both species: lymphoid depletion; hypocellularity of the bone marrow with associated anemia and thrombocytopenia; GI mucosal atrophy, erosion, and ulceration; degeneration of the testicular seminiferous epithelium; and mild to moderate hyperglycemia. These toxicities is reversible[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MV-4-11 cells
濃度 --
反応時間 4 h
実験の流れ

MV-4-11 cells were plated at 10,000 cells/well in 96-well plates containing compounds in 100 μL RPMI medium supplemented with 10% FBS. Cells were incubated with compound for 4 hours at 37◦C and 5% CO2 prior to analysis of MYC transcript levels. Inhibition was calculated relative to DMSO treated MYC levels.
動物実験 動物モデル mouse xenograft model using MV-4-11 acute myeloid leukemia cells
投薬量 15 mg/kg twice daily
投与方法 s.c.

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：

Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs [ Inflammation, 2022, 45(3):1388-1401] PubMed: 35301634
Targeting BET Proteins BRD2 and BRD3 in Combination with PI3K-AKT Inhibition as a Therapeutic Strategy for Ovarian Clear Cell Carcinoma [ Mol Cancer Ther, 2021, 20(4):691-703] PubMed: 33509905
Targeting BET proteins BRD2 and BRD3 in combination with PI3K-AKT inhibition as a therapeutic strategy for ovarian clear cell carcinoma [ Mol Cancer Ther, 2021, molcanther.0809.2020] PubMed: 33509905
Ex Vivo Culture Models of Hidradenitis Suppurativa for defining molecular pathogenesis and treatment efficacy of novel drugs [ bioRxiv, 2021, 10.1101/2021.10.11.464007] PubMed: N/A
Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation [ Cancer Cell, 2020, 37(4):584-598.e11] PubMed: 32220301

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。