1. Epigenetics
  2. Epigenetic Reader Domain

GSK1324726A (Synonyms: I-BET726)

Cat. No.: HY-13960 Purity: 98.21%
Data Sheet SDS Handling Instructions

GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC50=41 nM), BRD3 (IC50=31 nM), and BRD4 (IC50=22 nM).

For research use only. We do not sell to patients.
GSK1324726A Chemical Structure

GSK1324726A Chemical Structure

CAS No. : 1300031-52-0

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $165 In-stock
5 mg $150 In-stock
10 mg $200 In-stock
50 mg $650 In-stock
100 mg $990 In-stock
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    GSK1324726A purchased from MCE. Usage Cited in: J Med Chem. 2017 Jun 22.

    Protein degradation profile of VHL-based BET degraders. Sub-confluent HeLa cells are treated for 24 h with varying concentration of test compounds JQ1(Compound 3), I-BET726 (Compound 4). Protein extracts are separated by SDS-PAGE and then analyzed by Western blot. Proteins Brd4, Brd3, Brd2 and β-actin are probed for JQ1and I-BET726 with specific antibodies.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC50=41 nM), BRD3 (IC50=31 nM), and BRD4 (IC50=22 nM).

    IC50 & Target

    IC50: 22 nM (BRD4), 31 nM (BRD3), 41 nM (BRD2)[1]

    In Vitro

    A panel of neuroblastoma cell lines are treated with GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. All neuroblastoma cell lines tested exhibit potent growth inhibition, with a median growth IC50 value (gIC50; inhibitor concentration resulting in 50% growth inhibition) equal to 75 nM[1].

    In Vivo

    GSK1324726A (I-BET726) inhibits neuroblastoma tumor growth. In the SK-N-AS model, mice in the vehicle group are euthanized on day 14 due to large tumor size. While there is no significant difference in tumor growth between the vehicle and GSK1324726A (5 mg/kg) group, 58% tumor growth inhibition (TGI) is observed in the GSK1324726A (15 mg/kg) group on day 14 of the study (n=9; p=0.006). Mice in the GSK1324726A (15 mg/kg) group are treated for an additional 7 days before tumor volume reaches a level comparable to that observed in the vehicle group, at which point the study is terminated. Tumors in the CHP-212 model grow much more slowly. After 42 days, tumors in vehicle-treated mice are only half the size those in the SK-N-AS model at the end of the study (Day 14). In the CHP-212 model, treatment with 5 mg/kg GSK1324726A results in TGI equal to 50% (n=8; p=0.1816), and mice in the 15 mg/kg group exhibits a TGI of 82% at the end of the study (n=5; p=0.0488)[1].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.2993 mL 11.4966 mL 22.9933 mL
    5 mM 0.4599 mL 2.2993 mL 4.5987 mL
    10 mM 0.2299 mL 1.1497 mL 2.2993 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    GSK1324726A (I-BET726) is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

    Cell line growth-death assays are performed with a few modifications. Briefly, cells are seeded into 384-well or 96-well plates at a density optimized for 6 days of growth. The following day, T0 measurements are taken using CellTiter-Glo, CellTiter-Fluor, or CyQuant Direct. Plates are read on an Envision, Safire 2, or SpectraMax Gemini EM plate reader. Remaining plates are treated with DMSO or a titration of GSK1324726A. Cells are incubated for 6 days and developed. Results are plotted as a percentage of the T0 value, normalized to 100%, versus concentration of compound. A 4-parameter equation is used to generate concentration response curves. Growth IC50 (gIC50) values are calculated at the mid-point of the growth window (between DMSO and T0 values). Ymin-T0 values are calculated by subtracting the T0 value (100%) from the Ymin value on the curve, and are a measure of net population cell growth or death[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1][2]

    GSK1324726A (I-BET726) formulated as a spray dried dispersion is prepared as a suspension in 1% methylcellulose vehicle (Mice)[1].
    GSK1324726A (I-BET726) is formulated in DMSO and 10% (w/v) KleptoseTM in saline (2%:98%) at a concentration of 0.2 mg/mL (Rat)[2].

    Mice[1]
    CHP-212 (1×107) or SK-N-AS (5×106) cells in 100% matrigel are implanted subcutaneously into the right flank of approximately 9 week old female nude (Crl:CD-1-Foxn1 nu) mice. Tumors are measured with calipers and randomized using stratified sampling according to tumor size into treatment groups of 10 mice. GSK1324726A in vehicle or vehicle alone is administered orally by individual body weight at 10mls/kg. Mice are weighed and tumors are measured with calipers twice weekly, and mice are observed daily for any adverse treatment affects. Mice are euthanized using CO2 inhalation according to AVMA guidelines after two consecutive tumor measurements greater than 2500mm3, or if body weight loss greater than 20% is observed. For mouse pharmacodynamic studies, mice are euthanized as described above. Tumors are harvested from euthanized mice and placed in RNAlater for RNA isolation. Blood is collected after euthanasia via cardiac puncture.
    Rat[2]
    Male CD rats (253-283 g) are surgically prepared with implanted cannulae in the femoral vein (for GSK1324726A administration) and jugular vein (for blood sampling). Each rat receives Duphacillin (100 mg/kg s.c.) and Carprofen (7.5 mg/kg s.c.) as a pre-operative antibiotic and analgesic respectively. Each rat is allowed to recover for at least 2 days prior to dosing. Rats have free access to food and water throughout. Rat PK studies are conducted as a crossover design over 2 dosing occasions, with 3 days between dose administrations. Serial blood samples are taken (via indwelling jugular cannula) up to 26 h post dose administration on both dosing occasions. On study day 1, n=3 male rats each receives a 1 h intravenous infusion of GSK1324726A formulated in DMSO and 10% (w/v) KleptoseTM in saline (2%:98%) at a concentration of 0.2 mg/mL and the dose is filtered using a ca. 0.2 μm syringe filter unit. GSK1324726A is administered as a 1 h i.v. infusion at 5 mL/kg/h to achieve a target dose of 1 mg/kg. On study day 2, the same three rats each receives an oral administration of GSK1324726A suspended in 3% Pharmacoat 603/0.2% Sodium Lauryl Sulphate (w/v) aq. at a concentration of 0.6 mg/mL administered by gavage at 5 mL/kg to achieve a target dose of 3 mg/kg. At the end of the study the rats are euthanised by administration of sodium pentobarbital through the jugular vein cannula. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    434.91

    Formula

    C₂₅H₂₃ClN₂O₃

    CAS No.

    1300031-52-0

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 46 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 98.21%

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    Product Name:
    GSK1324726A
    Cat. No.:
    HY-13960
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