Molibresib (I-BET-762)

製品コードS7189 バッチS718902

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) 84 mg/mL (198.15 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)は、IC50が約35 nMのBETタンパク質阻害剤であり、マクロファージによる炎症誘発性タンパク質の産生を抑制し、急性炎症を阻害し、他のブロモドメイン含有タンパク質に対して高い選択性を示します。
in vitro Molibresib (I-BET-762) is an inhibitor for BET (bromodomain and extra terminal domain) proteins, BRD2, BRD3 and BRD4, which binds to the tandem bromodomains of BET with Kd of 50.5–61.3 nM and 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 their binding to acetylated histones, thus disrupting the formation of chromatin complexes essential for expression of inflammatory genes. Treatment with it during the first 2 d of differentiation alters CD4+ T-cell cytokine production, up-regulating expression of several antiinflammatory gene products and down-regulating expression of several proinflammatory cytokines.
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, and twice-daily injections for 2 days protect them against death caused by sepsis. 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).

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, the 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
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
BRD4 promotes resection and homology-directed repair of DNA double-strand breaks [ Nat Commun, 2022, 13(1):3016] PubMed: 35641523
Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL [ Mol Syst Biol, 2022, 18(8):e10855] PubMed: 35959629

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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