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Molibresib (I-BET-762)

For research use only.

Catalog No.S7189 Synonyms: GSK525762, GSK525762A

17 publications

Molibresib (I-BET-762) Chemical Structure

CAS No. 1260907-17-2

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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10mM (1mL in DMSO) GBP 292 In stock
GBP 185 In stock
GBP 384 In stock
GBP 958 In stock
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Selleck's Molibresib (I-BET-762) has been cited by 17 publications

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  • PECAPJ49 parental and cetuximab-resistant clones were treated with 100 nmol/L cetuximab ± 800 nmol/L I-BET-762(IBET) for 72 hours. Cells were stained with crystal violet and quantified as described in Materials and Methods (n = 3; *, P < 0.02). Figures are representative of three independent experiments.

    Cancer Res, 2018, 78(15):4331-4343. Molibresib (I-BET-762) purchased from Selleck.

  • A., B. and C. Dose response curves of MPNST-derived cell lines treated with three bromodomain inhibitors: JQ1, OTX015 and I-BET-762.

    Oncotarget, 2016, 7(24):35753-35767. Molibresib (I-BET-762) purchased from Selleck.

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

Biological Activity

Description 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.
Targets
BET proteins [1]
(Cell-free assay)
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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TY82 NWfkOHZITnWwY4Tpc44h[XO|YYm= NF3XbFkxNjJidH:gNUB2VQ>? MUeyOEBpenN? NYLQTIxXUW6qaXLpeIlwdiCxZjDCVmQ1KGmwIHj1cYFvKFS\OEKgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGNvTYnjJJBzd3SnaX6g[ZhxemW|c3nvckBifCByLkKgeI8hOSC3TTDh[pRmeiB{NDDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NHfKRYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWyOVQ{PSd-Mkm1NlU1OzV:L3G+
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TY82 or NCI-H1299 Mn;CSpVv[3Srb36gZZN{[Xl? NHfhOXQxNjJidH:gNUB2VQ>? M4P3clI1KGi{cx?= Mmq2TY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJHR[QDJib4KgUmNKNUhzMkm5JINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCSRD3MNUBxem:2ZXnuJIV5eHKnc4Ppc44h[XRiMD6yJJRwKDFidV2gZYZ1\XJiMkSgbJJ{KGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NFPifm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUWyOVQ{PSd-Mkm1NlU1OzV:L3G+
TY82 or NCI-H1299 NFTDPXZHfW6ldHnvckBie3OjeR?= Ml36NE4zKHSxIEGgeW0> MmfyNlQhcHK| MWrJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gWHk5OiCxcjDOR2kuUDF{OUmgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKFCGLVyxJI1TVkFiZYjwdoV{e2mxbjDheEAxNjJidH:gNUB2VSCjZoTldkAzPCCqcoOgZpkhWlRvUFPSJIFv[Wy7c3nz M4joe|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUK1OFM2Lz5{OUWyOVQ{PTxxYU6=
C4-2B M{LacmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NGrMOlA6PiCqcoO= M3S4fWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ{StNmIh[2WubIOgZYZ1\XJiOU[gbJJ{KGK7IFPlcIwuXGm2ZYKg[4xwKHKnYXflcpQh[mG|ZXSgcJVucW6nc3PlcoNmKGG|c3H5 M3rMXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUSxN|cyLz5{OUW0NVM4OTxxYU6=
22Rv1 MnWzRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M2PTbFk3KGi{cx?= MXTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKDJ{Uo[xJINmdGy|IHHmeIVzKDl4IHjyd{BjgSCFZXzsMXRqfGW{IHfsc{Bz\WGpZX70JIJie2WmIHz1cYlv\XOlZX7j[UBie3OjeR?= NYi3NZhSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1OFE{PzFpPkK5OVQyOzdzPD;hQi=>
LNCAP M1rXTGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MmCxPVYhcHK| NH61O4NCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzOR2FRKGOnbHzzJIFnfGW{IEm2JIhzeyCkeTDD[YxtNVSrdHXyJIdtdyC{ZXHn[Y51KGKjc3XkJIx2dWmwZYPj[Y5k\SCjc4PhfS=> MnTIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl3NEGzO|EoRjJ7NUSxN|cyRC:jPh?=
HL60 NIrxRYtEgXSxdH;4bYNqfHliYYPzZZk> M1uyRWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhNPjBiY3XscJMh[nliTWTTJIF{e2G7LDDJR|UxKD1iMD6xNkDPxE1w M3rncFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkW3NFk6Lz5{OU[1O|A6QTxxYU6=
Raji M4DKUmZ2dmO2aX;uJIF{e2G7 MU\Jcohq[mm2aX;uJI9nKEKUREStRmQyKGmwIHj1cYFvKFKjanmgZ4VtdHNiYYPz[ZN{\WRiYYOg[I94dnKnZ4XsZZRqd25ib3[gUXlEKGenbnWg[ZhxemW|c3nvckBjgSCSQ2KgcYV1cG:mLDDJR|UxKD1iMD6xN|Ih|ryPLh?= M1\LO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkW3NFk6Lz5{OU[1O|A6QTxxYU6=
LNCAP MUTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NWfT[mF4SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDMUmNCWCClZXzsd{whUUN3MDC9JFAvOzV4NTFOwG0v M17odFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7N{W4OVE5Lz5{OUe1PFUyQDxxYU6=
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Growth inhibition assay
Cell viability ; 

PubMed: 26840085     


A., B. and C. Dose response curves of MPNST-derived cell lines treated with three bromodomain inhibitors: JQ1, OTX015 and I-BET-762.

26840085
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]

Protocol

Kinase Assay:[1]
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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 Research:[2]
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  • 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Mouse
  • Dosages: 30 mg/kg
  • Administration: i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 84 mg/mL (198.15 mM)
Ethanol 42 mg/mL warmed (99.07 mM)
Water 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 Information

Molecular Weight 423.9
Formula

C22H22ClN5O2

CAS No. 1260907-17-2
Storage powder
in solvent
Synonyms GSK525762, GSK525762A
Smiles CCNC(=O)CC1C2=NN=C(N2C3=C(C=C(C=C3)OC)C(=N1)C4=CC=C(C=C4)Cl)C

In vivo Formulation Calculator (Clear solution)

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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
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    C4=C3/X C4: LOG(C4):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03266159 Withdrawn Drug: GSK525762 Besylate tablets|Drug: Trametinib tablets Solid Tumours GlaxoSmithKline November 27 2017 Phase 2
NCT02964507 Active not recruiting Drug: GSK525762|Drug: Placebo|Drug: Fulvestrant Neoplasms GlaxoSmithKline February 2 2017 Phase 2
NCT01943851 Completed Drug: GSK525762 Neoplasms GlaxoSmithKline May 14 2014 Phase 2
NCT01587703 Completed Drug: GSK525762 Carcinoma Midline GlaxoSmithKline March 28 2012 Phase 1

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.

Handling Instructions

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Epigenetic Reader Domain Signaling Pathway Map

Epigenetic Reader Domain Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID