Antibodies
I-BET-762
- 貨號 Cat. No.
- S7189
- 規格 Size
- 10mgã€50mg
- 品牌 Brand
- Selleckchem
Description
I-BET-762
Catalog No.S7189
I-BET-762 is an inhibitor for BET proteins with IC50 of ~35 nM, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | I-BET-762 is an inhibitor for BET proteins with IC50 of ~35 nM, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins. | |||||
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| Targets | BET proteins | |||||
| IC50 | 35 nM [1] | |||||
| 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] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Fluorescence resonance energy transfer (FRET) titrations | 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). |
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Cell Assay: [2]
| Cell lines | CD4+ T cells |
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| Concentrations | ~500 nM |
| Incubation Time | 60–72 h |
| Method | 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. |
Animal Study: [1]
| Animal Models | Mouse |
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| Dosages | 30 mg/kg |
| Administration | i.v. |
References
Chemical Information
| Molecular Weight (MW) | 423.9 |
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| Formula | C22H22ClN5O2 |
| CAS No. | 1260907-17-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | GSK525762, GSK525762A |
| Solubility (25°C) * | In vitro | DMSO | 85 mg/mL (200 mM) |
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| Water | 11 mg/mL (25 mM) | ||
| Ethanol | 85 mg/mL (200 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. | |||
| Chemical Name | 4H-[1,2,4]Triazolo[4,3-a][1,4]benzodiazepine-4-acetamide, 6-(4-chlorophenyl)-N-ethyl-8-methoxy-1-methyl-, (4S)- |
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