1. PI3K/Akt/mTOR
  2. PI3K

BAY 80-6946 (Synonyms: Copanlisib)

Cat. No.: HY-15346 Purity: 98.09%
Data Sheet SDS Handling Instructions

BAY 80-6946 is an ATP-competitive selective class-I PI3 kinases inhibitor, with IC50s of 0.5, 0.7, 3.7 and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, and much less active against mTOR (IC50=45 nM) and other PIKs (no inhibition at 1 μM).

For research use only. We do not sell to patients.
BAY 80-6946 Chemical Structure

BAY 80-6946 Chemical Structure

CAS No. : 1032568-63-0

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    BAY 80-6946 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    BAY 80-6946 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    BAY 80-6946 is an ATP-competitive selective class-I PI3 kinases inhibitor, with IC50s of 0.5, 0.7, 3.7 and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, and much less active against mTOR (IC50=45 nM) and other PIKs (no inhibition at 1 μM).

    IC50 & Target

    IC50: 0.5 nM (PI3Kα), 0.7 nM (PI3Kδ), 3.7 nM (PI3Kβ), 6.4 nM (PI3Kγ), 45 nM (mTOR)[1]

    In Vitro

    BAY 80-6946 potently inhibits the catalytic activity of the class I PI3Kα, β, γ, and δ isoforms with IC50s of 0.5, 3.7, 6.4, and 0.7 nM, respectively. BAY 80-6946 shows significantly weaker activity against mTOR with an IC50 of 45 nM. In KPL4 cells, BAY 80-6946 reduces basal levels of AKT phosphorylation at both Thr308 and Ser473 with IC50 values of 0.4 and 0.6 nM, respectively. BAY 80-6946 has mean IC50 values of 19 nM against cell lines with PIK3CA-activating mutations (n = 9) and 17 nM against HER2-positive cell lines (n=7), whereas the activity in PIK3CA wild-type and HER2-negative cells is about 40-fold less potent (average IC50=774 nM; n=11)[1].

    In Vivo

    BAY 80-6946 is highly efficacious in a variety of human tumor xenograft models derived from different tumor indications that exhibit an activated PI3K pathway. BAY 80-6946 is administered at 0.5 to 6 mg/kg i.v. every second day for a total of five doses starting on day 14, following tumor cell implantation. On day 25, 3 days after the last dose, TGI rates of 77%, 84%, 99%, and 100% are observed with BAY 80-6946 at doses of 0.5, 1, 3, and 6 mg/kg, respectively. Complete tumor regression is shown in 10 of 10 rats in the 3 and 6 mg/kg groups, and all rats remained tumor free at the termination of the study on day 73. Tumor growth delays more than 25 days are observed in the 0.5 and 1 mg/kg dose groups[1].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.0811 mL 10.4054 mL 20.8108 mL
    5 mM 0.4162 mL 2.0811 mL 4.1622 mL
    10 mM 0.2081 mL 1.0405 mL 2.0811 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    The effect of BAY 80-6946 on PI3Kα, PI3Kβ, and PI3Kγ activity is measured by the inhibition of 33P incorporation into phosphatidylinositol. The effect of BAY 80-6946 on PI3Kδ is determined by Upstate/Chemicon using their proprietary PIProfiler assay system that uses homogeneous time-resolved fluorescence to measure inhibition of kinase activity. The effect of BAY 80-6946 on PI4K-II, PIP4-5K, and PIP5-4K is measured using assay conditions nearly identical to those for measuring PI3K activity, except that the p110 protein is replaced with either recombinant PI4K-II protein or PIP4-5K protein, respectively. In addition, PIP4 and PIP5 are used as the lipid substrate in place of phosphatidylinositol in the PIP4-5K and PIP5-4K assays, respectively[1].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    BAY 80-6946 is dissolved in DMSO/Trifluoroacetic acid[1].

    The 5 mM stock solution of BAY 80-6946 (in DMSO with 10 mM trifluoroacetic acid) is used. The cell lines are maintained in RPMI-1640 medium containing 10% heat-inactivated fetal calf serum. Cell proliferation is determined using the CellTiter-Glo Luminescent Cell Viability Kit[1].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    BAY 80-6946 is dissolved in a PEG400/acidified water (0.1 N HCl, pH 3.5; 20/80, v/v) or 5% mannitol vehicle (Mice and Rat)[1].

    Mice and Rat[1]
    The in vivo antitumor efficacy of BAY 80-6946 is assessed in athymic nude rats or nude mice using xenograft models of human tumors. Animals are housed according to institutional guidelines with access to food (pelleted diet) and water ad libitum. Studies with patient-derived tumors are conducted in EPO GmbH or in Oncotest GmbH with written formed consent from each patient and the approval from local ethical committees. Tumor xenografts are generated by harvesting cells from mid-log phase cultures and injecting subcutaneously into the right flank of each rat and mouse. BAY 80-6946 is dissolved in a PEG400/acidified water (0.1 N HCl, pH 3.5; 20/80, v/v) or 5% mannitol vehicle. Treatment is initiated when all animals in an experiment had established tumors. BAY 80-6946 is administered every second day, every third day, or weekly via an intravenous bolus at the indicated doses. Tumor dimensions and body weights are recorded twice weekly starting on the first day of treatment. Tumor volumes are calculated. Antitumor efficacy is determined as a function of tumor growth inhibition (% TGI). TGI is calculated.
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    480.52

    Formula

    C₂₃H₂₈N₈O₄

    CAS No.

    1032568-63-0

    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

    10 mM in DMSO

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

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    Product Name:
    BAY 80-6946
    Cat. No.:
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