5.06071

I-BET

InSolution, ≥98%, 50 mM in DMSO, A cell-permeable benzodiazepine compound

• Synonym(s): InSolution I-BET, ( S)-2-(6-(4-Chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-ethylacetamide, (S)-2-(6-(4-Chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-ethylacetamide
• Empirical Formula (Hill Notation): C₂₂H₂₂ClN₅O₂
• CAS Number: 1260907-17-2
• Molecular Weight: 423.90
• MDL number: MFCD22417091
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• assay: ≥98% (HPLC)
• form: liquid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; avoid repeated freeze/thaw cycles; desiccated (hygroscopic); protect from light
• storage temp.: −70°C
• InChI: 1S/C22H22ClN5O2/c1-4-24-20(29)12-18-22-27-26-13(2)28(22)19-10-9-16(30-3)11-17(19)21(25-18)14-5-7-15(23)8-6-14/h5-11,18H,4,12H2,1-3H3,(H,24,29)/t18-/m0/s1
• InChI key: AAAQFGUYHFJNHI-SFHVURJKSA-N

Description

General description

A cell-permeable benzodiazepine compound that binds the tandem bromodomains of BET (bromodomain and extra terminal domain) family members BRD2 (1-473), BRD3 (1-434), and BRD4 (1-477) with high affinity (K_d = 61.3, 50.5, and 55.2 nM, respectively, by ITC) and effectively competes against tetra-acetylated H4 peptide (Millipore cat. no. 12-379) for BRD2/3/4 binding (IC₅₀ = 32.5, 42,4, and 36.1 nM, respectively, in competitive equilibrium binding assays), while exhibiting little affinity toward 5 other bromodomain-containing proteins (ATAD2, BAZ2B, CREBBP, PCAF, SP140) or a panel of 38 cellular enzymes, GPCRs, transporters, and ion channels. Shown to differentially modulate LPS-induced gene expression, notably suppressing LPS-induced upregulation of genes involved in inflammatory response, in murine BMDMs (bone marrow-derived macrophages) in vitro (30 min 1 µM pretreatment) and effectively prevent LPS-, heat-killed Salmonella typhimurium-, and CLP- (caecal ligation and puncture) induced death in mice in vivo (30 mg/kg i.v.). Cellular Brd2/3/4 knockdown using siRNA results in mostly the same effect as I-BET treatment in modulating LPS gene induction profile in murine BMDMs, but not without exceptions, indicating that not all BET-dependent transcription regulations are mediated via its binding to acetylated histones.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
tandem bromodomains of BET

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Physical form

A 50 mM (5 mg/236 µL) sterile-filtered solution of I-BET (Cat. No. 401010) in DMSO.

Reconstitution

Following initial thaw, aliquot and freeze (-20°C). Aliquots are stable for up to 6 months at -20°C.

Other Notes

Nicodeme, E., et al. 2010. Nature468, 1119.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 10 - Combustible liquids
• wgk_germany: WGK 2
• flash_point_f: 188.6 °F - (refers to pure substance)
• flash_point_c: 87 °C - (refers to pure substance)