1. PI3K/Akt/mTOR
  2. PI3K

BAY 80-6946 (Synonyms: BAY80-6946; 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, δ, β and γ, 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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10 mM * 1 mL in DMSO $165 In-stock
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10 mg $240 In-stock
50 mg $600 In-stock
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  • Biological Activity

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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, δ, β and γ, 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)[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)[2].

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[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02369016 Bayer Lymphoma, Non-Hodgkin September 22, 2015 Phase 3
NCT02367040 Bayer Lymphoma,Non-Hodgkin August 3, 2015 Phase 3
NCT02626455 Bayer Lymphoma, Non-Hodgkin January 6, 2016 Phase 3
NCT01404390 Bayer Neoplasms August 2011 Phase 1
NCT01411410 Bayer Neoplasms August 2011 Phase 1
NCT00962611 Bayer Neoplasms November 2009 Phase 1
NCT01660451 Bayer Lymphoma, Non-Hodgkin November 19, 2012 Phase 2
NCT02253420 Bayer Medical Oncology October 8, 2014 Phase 1
NCT02391116 Bayer Diffuse Large-Cell Lymphoma May 8, 2015 Phase 2
NCT02155582 Bayer Non Hodgkin Lymphoma August 12, 2014 Phase 1
NCT02119221 Bayer Healthy Volunteers February 2014 Phase 1
NCT02342665 Bayer Lymphoma Non-Hodgkin April 21, 2015 Phase 1|Phase 2
NCT03172884 Bayer Hepatic Insufficiency June 6, 2017 Phase 1
NCT02455297 Bayer Lymphoma, Mantle-Cell August 2015 Phase 2
NCT01460537 Bayer Neoplasms November 2011 Phase 1
NCT02822482 UNICANCER Carcinoma, Squamous Cell of Head and Neck June 2016 Phase 1|Phase 2
NCT03052933 Chonnam National University Hospital|Bayer|Consortium for Improving Survival of Lymphoma Mature T-Cell and NK-Cell Neoplasm May 2017 Phase 1|Phase 2
NCT02728258 NRG Oncology|National Cancer Institute (NCI) Endometrial Endometrioid Adenocarcinoma|Endometrial Mixed Adenocarcinoma|Endometrial Serous Adenocarcinoma|Endometrial Undifferentiated Carcinoma|Metastatic Endometrioid Adenocarcinoma|PIK3CA Gene Mutation|Recurrent Uterine Corpus Carcinoma September 2016 Phase 2
NCT02705859 Cancer Trials Ireland HER2 Positive Breast Cancer April 2016 Phase 1
NCT02631590 H. Lee Moffitt Cancer Center and Research Institute|Bayer Biliary Carcinoma|Gall Bladder Carcinoma|Cholangiocarcinoma|Gastrointestinal Tumor June 28, 2016 Phase 2
NCT03128619 Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI)|Bayer Estrogen Receptor Positive|HER2/Neu Negative|Invasive Breast Carcinoma|Multifocal Breast Carcinoma|Postmenopausal|Progesterone Receptor Positive|Stage I Breast Cancer|Stage IA Breast Cancer|Stage IB Breast Cancer|Stage II Breast Cancer|Stage IIA Breast Cancer|Stage IIB Breast Cancer|Stage III Breast Cancer|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer|Stage IV Breast Cancer August 1, 2017 Phase 1|Phase 2
NCT01392521 Bayer Neoplasms July 2011 Phase 1
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References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
Kinase Assay
[2]

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[2].

Cell Assay
[1]

BAY 80-6946 is dissolved in DMSO/5 mM Trifluoroacetic acid[1].

BT-474 cells are plated at 4.5 million cells per 10-cm plate and grown in triplicate, then treated with drug the following day. At indicated times, cells are washed three times with PBS, trypsinized, and resuspended in media. Cells are mixed with trypan blue, and the number of viable cells is determined using the Beckman ViCellXR[1].

Animal Administration
[2]

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)[2].

Mice and Rat[2]
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.

References
M.Wt

480.52

Formula

C₂₃H₂₈N₈O₄

CAS No.

1032568-63-0

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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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BAY 80-6946
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