Molibresib (I-BET-762)

製品コードS7189 バッチS718903

印刷

化学情報

Chemical Structure Synonyms GSK525762, GSK525762A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H22ClN5O2
分子量 423.9 CAS No. 1260907-17-2
Solubility (25°C)* 体外 DMSO 84 mg/mL (198.15 mM)
Ethanol (warmed with 50ºC water bath) 42 mg/mL (99.07 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.
* <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 Molibresib (I-BET-762, GSK525762, GSK525762A) is an inhibitor for BET proteins with IC50 of ~35 nM in a cell-free assay, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins.
in vitro Molibresib (I-BET-762) is an inhibitor for BET (bromodomain and extra terminal domain) proteins, BRD2, BRD3 and BRD4. It binds to the tandem bromodomains of BET with Kd of 50.5–61.3 nM, displaces a tetra-acetylated H4 peptide prebound to tandem bromodomains of BET with IC50 of 32.5–42.5 nM in FRET analysis. This compound occupies the acetyl-lysine binding pocket of BET proteins and inhibits binding of BET proteins to acetylated histones, thus disrupts the formation of the chromatin complexes essential for expression of inflammatory genes. [1] Its treatment during the first 2 d of differentiation alters CD4+ T-cell cytokine production, up-regulated expression of several antiinflammatory gene products and down-regulated expression of several proinflammatory cytokines. [2]
in vivo Molibresib (I-BET-762) confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis. A single dose of this compound applied at 1.5 h after LPS injection cures the mice. Twice-daily injections of I-BET for 2 days protects mice against death caused by sepsis. [1] Limited treatment with it exclusively during early priming inhibited the ability of Th1-differentiated 2D2 T cells to induce neuroinflammation in a mouse model of experimental autoimmune encephalomyelitis (EAE). [2]

プロトコル(参考用のみ)

キナーゼアッセイ Fluorescence resonance energy transfer (FRET) titrations
Fluorescence resonance energy transfer (FRET) titrations. Molibresib (I-BET-762) is titrated against BRD2 (200 nM), BRD3 (100 nM) and BRD4 (50 nM) in 50 mM HEPES pH7.5, 50 mM NaCl, 0.5 mM CHAPS in the presence of tetra-acetylated Histone H4 peptide (200 nM). After equilibrating for 1 hour, the bromodomain protein : peptide interaction is detected using FRET following the addition of 2nM Europium cryptate labelled streptavidin and 10 nM XL-665-labelled anti-6His antibody in assay buffer containing 0.05% (v/v) BSA and 400 mM KF. Plates are read using an Envision Plate reader (excitation 320 nm, emission 615 nm and 665 nm).
細胞アッセイ 細胞株 CD4+ T cells
濃度 ~500 nM
反応時間 60–72 h
実験の流れ CD4+ T cells are isolated from lymph nodes and spleens of 10- to 12-wk old mice and activated with plate bound anti-CD3 and anti-CD28 antibodies in the presence of indicated cytokines. During the 60–72 h of initial activation, Molibresib (I-BET-762) is included. Over the course of 5 d of T-cell culture and expansion, this compound is diluted 12-fold relative to the starting concentrations.
動物実験 動物モデル Mouse
投薬量 30 mg/kg
投与方法 i.v.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21068722/
  • https://pubmed.ncbi.nlm.nih.gov/22912406/

カスタマーフィードバック

Data from [Data independently produced by , , Cancer Res, 2018, 78(15):4331-4343]

Data from [Data independently produced by , , Oncotarget, 2016, 7(24):35753-35767]

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：

Bromodomain Protein Inhibition Protects β-Cells from Cytokine-Induced Death and Dysfunction via Antagonism of NF-κB Pathway [ Cells, 2024, 13(13)1108] PubMed: 38994961
BET inhibition revealed varying MYC dependency mechanisms independent of gene alterations in aggressive B-cell lymphomas [ Clin Epigenetics, 2024, 16(1):185] PubMed: 39702340
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Regulation of the WNT-CTNNB1 signaling pathway by severe fever with thrombocytopenia syndrome virus in a cap-snatching manner [ mBio, 2023, e0168823.] PubMed: 37882780
High-Content and High-Throughput Clonogenic Survival Assay Using Fluorescence Barcoding [ Cancers -Basel), 2023, 15(19)4772] PubMed: 37835466
Pan-cancer analysis of super enhancer-induced PRR7-AS1 as a potential prognostic and immunological biomarker [ Front Genet, 2023, 14:1160599] PubMed: 37091809
Exploration de la réponse moléculaire à l'inhibition des protéines BET dans les lymphomes B réfractaires [ HAL OPEN SCIENCE, 2023, ] PubMed: None
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272

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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