Antibodies
BAY 80-6946 (Copanlisib)
- 貨號 Cat. No.
- S2802
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
BAY 80-6946 (Copanlisib)
BAY 80-6946 is a potent and highly selective reversible PI3K inhibitor for PI3Kα/β with IC50 of 0.469 nM/3.72 nM. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | BAY 80-6946 is a potent and highly selective reversible PI3K inhibitor for PI3Kα/β with IC50 of 0.469 nM/3.72 nM. Phase 1. | |||||
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| Targets | PI3Kα | PI3Kβ | ||||
| IC50 | 0.469 nM | 3.72 nM [1] | ||||
| In vitro | BAY 80-6946 is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. BAY 86-9766 inhibits proliferation with IC50 of 147 nM in HuCCT-1 (KRASG12D ) and 137 nM in EGI-1 (KRASG12D ) cell lines. [2] | |||||
| In vivo | BAY 80-6946 is generally well tolerated through the MTD (maximum tolerated dose) of 0.8 mg/kg. PK (pharmacokinetics) results support weekly dosing. Grade 2/3 hyperglycemia in the first 24 hrs after receiving a dose is common at the MTD. PK, clinical SD and FDG-PET data are consistent with effective exposure and PI3K pathway inhibition. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| PI3Kα and PI3Kβ Radioactive Lipid Kinase Assay | The p110α biochemical assay is a radioactive assay measuring the incorporation of 33P into the p110α substrate, phosphatidylinositol (PI). A His-tagged N-terminal truncated (ΔN 1-108) p110α and the same truncated p110β (ΔN 1-108) proteins lacking the p85-binding domain is expressed in Sf9 cells and purified to ＞50% purity. For the generation of IC50, the reaction is performed in a 384-well format using MaxiSorp plates under the following conditions. Plates are coated with 2 μg/well of a 1:1 molar ratio of phosphatidylinositol (PI) and phosphatidylserine (PS) diluted in chloroform. The organic solvent is allowed to evaporate by storing plates in the fume hood overnight. Plates are then sealed with mylar plate sealers and stored up to a month at 4 ℃ until needed. 7.5 ng truncated p110α protein is added to each well, containing 9 μL of reaction buffer (50mM MOPSO pH 7.0, 100 mM NaCl, 4mM MgCl2, 0.1%(w/v)BSA) except for negative control wells which received reaction buffer only. One microliter of each test compound in DMSO is transferred from stock dilutions to generate an eight-point dose response (0.0, 0.003, 0.01, 0.03, 0.1, 0.3, 1.0, 3.0 and 10 μM final BAY compound concentration). Reactions are started by the addation of a 40 μM ATP solution containing 20 μCi/mL [γ-33P]-ATP and are allowed to proceed for two hours at room temperature with gentle mixing. Reactions are terminated by the addition of 5μL of a 25 mM EDTA stock solution. Plates are washed with a 384-well plate washer in buffer without detergent and 25μL of UltimaGold scintillation cocktail is added to each well. The radioactivity incorporated into the immobilized PI substrate is determined with a BetaPlate Liquid Scintillation Counter. |
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Cell Assay: [2]
| Cell lines | KPL4, BT474, T47D, BT20, MCF7, MDA-MB-468, SK-Br-3, LNCaP, PC3, Colo205, HT29, HCT116, A549, H460, U87MG and 786O cells |
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| Concentrations | ~10 μM |
| Incubation Time | 72 hours |
| Method | Cell proliferation is determined using the Cell Titer-Glo luminescent cell viability kit after 72 hours exposure to the drugs. Briefly, cells are plated at 500-1000 cells/well of 384-well plates in 25 μL growth medium. For each cell line assayed, cells are plated into a separate plate for determination of luminescence at the t = 0 hours and t = 72 hours time points. Following overnight incubation at 37 ℃, luminescence values for the t = 0 samples are determined by adding 25μL Cell Titer-Glo solution per well, transferring the plates to an orbital shaker for 10 minutes at room temperature, and then reading the plates on a Wallac Victor2 1420 Multilable HTS Counter using the luminometry window (maximum light detection is measured at 428 nM). Dose plates for t = 72 hour time points are treated with compounds diluted into growth medium in a final volume of 30 μL. Cells are then incubated for 72 hours at 37 ℃. Luminescence values for the t = 72 hour samples are determined by adding 30μL Cell Titer-Glo solution per well, placing the cells on a shaker for 10 minutes at room temperature, and then reading the luminescence using a Victor luminometer. For data processing, t = 0 values are subtracted from those determined for the t = 72 hour time points, for both the treated and untreated samples. Percent differences in luminescence between drug treated and controls are used to determine percent inhibition of growth. |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00962611 | Recruiting | Neoplasms | Bayer | 2009-11 | Phase 1 |
| NCT01404390 | Completed | Neoplasms | Bayer | 2011-08 | Phase 1 |
| NCT01411410 | Recruiting | Neoplasms | Bayer | 2011-08 | Phase 1 |
| NCT01460537 | Recruiting | Neoplasms | Bayer | 2011-11 | Phase 1 |
| NCT01660451 | Recruiting | Lymphoma, Non-Hodgkin | Bayer | 2012-11 | Phase 2 |
Chemical Information
Download BAY 80-6946 (Copanlisib) SDF
| Molecular Weight (MW) | 480.52 |
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| Formula | C23H28N8O4 |
| CAS No. | 1032568-63-0 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 0.002 mg/mL (<1 mM) |
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| Water | 0.002 mg/mL (<1 mM) | ||
| Ethanol | 0.01 mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or 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 Name | 5-Pyrimidinecarboxamide, 2-amino-N-[2,3-dihydro-7-methoxy-8-[3-(4-morpholinyl)propoxy]imidazo[1,2-c]quinazolin-5-yl]- |
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Customer Reviews (2)
 Click to enlarge | Rating | |
| Source | Dr Antonino Maria Spartà from University of Bologna. BAY 80-6946 (Copanlisib) purchased from Selleck | |
| Method | MTT | |
| Cell Lines | Jurkat E6.1 | |
| Concentrations | ||
| Incubation Time | 48 h | |
| Results | The compounds BAY80-6946 and TG100713, which are respectively an alpha/beta- and a pan-isoforms inhibitors, demonstrated a very good ability to block Jurkat E6.1 proliferation with an IC50 slightly higher than 1 mM. |
