I-BET-762

Catalog No.S7189

I-BET-762 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.

Price Stock Quantity  
USD 470 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

I-BET-762 Chemical Structure

I-BET-762 Chemical Structure
Molecular Weight: 423.9

Validation & Quality Control

Quality Control & MSDS

Epigenetic Reader Domain Inhibitors with Unique Features

  • Selective BET Inhibitor

    PFI-1 (PF-6405761) BRD4-selective, IC50=0.22 μM.

  • BET Inhibitor in Clinical Trial

    RVX-208 Phase II for Dyslipidemia.

  • Newest BET Inhibitor

    Bromosporine Broad spectrum inhibitor for bromodomains with IC50 of 0.41 μM, 0.29 μM, 0.122 μM and 0.017 μM for BRD2, BRD4, BRD9 and CECR2, respectively.

  • Classic BET Inhibitor

    I-BET151 (GSK1210151A) Novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM, respectively.

Product Information

  • Compare Epigenetic Reader Domain Inhibitors
    Compare Epigenetic Reader Domain Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description I-BET-762 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.
Targets BET proteins [1]
(Cell-free assay)
IC50 35 nM
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).

Cell Assay: [2]

Cell lines CD4+ T cells
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
Formulation 20% beta-cyclodextrin, 2% DMSO in 0.9% saline
Dosages 30 mg/kg
Administration i.v.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Nicodeme E, et al. Nature, 2010, 468(7327), 1119-1123.

[2] Bandukwala HS, et al. PNAS, 2012, 109(36), 14532-14537.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-05-07)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02706535 Not yet recruiting Drug Interactions GlaxoSmithKline May 2016 Phase 1
NCT01943851 Recruiting Cancer GlaxoSmithKline May 2014 Phase 1
NCT01587703 Recruiting Carcinoma, Midline GlaxoSmithKline March 2012 Phase 1

Chemical Information

Download I-BET-762 SDF
Molecular Weight (MW) 423.9
Formula

C22H22ClN5O2

CAS No. 1260907-17-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms GSK525762, GSK525762A
Solubility (25°C) * In vitro DMSO 84 mg/mL (198.15 mM)
Ethanol 42 mg/mL warmed (99.07 mM)
Water <1 mg/mL (<1 mM)
In vivo
* <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)-

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Epigenetic Reader Domain Products

Recently Viewed Items

Tags: buy I-BET-762 | I-BET-762 supplier | purchase I-BET-762 | I-BET-762 cost | I-BET-762 manufacturer | order I-BET-762 | I-BET-762 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us