受注:045-509-1970 |
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Synonyms | GSK525762, GSK525762A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C22H22ClN5O2 |
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分子量 | 423.9 | CAS No. | 1260907-17-2 | |
Solubility (25°C)* | 体外 | DMSO | 85 mg/mL (200.51 mM) | |
Ethanol | 85 mg/mL warmed with 50ºC water bath (200.51 mM) | |||
Water | 11 mg/mL (25.94 mM) | |||
* <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. |
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. |
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in vitro | I-BET-762 is an inhibitor for BET (bromodomain and extra terminal domain) proteins, BRD2, BRD3 and BRD4, 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. I-BET-762 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] I-BET-762 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 | I-BET-762 confers protection against lipopolysaccharide-induced endotoxic shock and bacteria induced sepsisa. Single dose of I-BET 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 I-BET-762 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] |
キナーゼアッセイ | Fluorescence resonance energy transfer (FRET) titrations | |
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Fluorescence resonance energy transfer (FRET) titrations. I-BET 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. I-BET-762 compounds is included during the 60–72 h of initial activation. Over the course of 5 d of T-cell culture and expansion, the compounds 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. |
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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]
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 |
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 |
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 |
Breaking boundaries: Pan BETi disrupt 3D chromatin structure, BD2-selective BETi are strictly epigenetic transcriptional regulators [ Biomed Pharmacother, 2022, 152:113230] | PubMed: 35687908 |
Insights into the roles and driving forces of CCT3 in human tumors [ Front Pharmacol, 2022, 13:1005855] | PubMed: 36313331 |
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。