| Size | Price | Stock | Qty |
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| 2mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Copanlisib (formerly BAY 80-6946; brand name: Aliqopa) is a potent, ATP-competitive and pan-class I PI3K (phosphoinositide 3-kinase) inhibitor with potential anticancer activity. According to cell-free assays for PI3Kα/β/γ/δ, it has IC50 values of 0.5, 3.7, 6.4, and 0.7 nM. Adult patients with relapsed follicular lymphoma who have had at least two prior systemic therapies are eligible to receive Copanlisib as of September 2017 per FDA approval. With IC50 values of 137 nM and 147 nM, respectively, in HuCCT-1 (KRASG12D) and EGI-1 (KRASG12D) cell lines, BAY 80-6946 demonstrated strong anti-proliferative activity. The maximum tolerated dose (MTD) for BAY 80-6946 is 0.8 mg/kg, and this dose is typically well tolerated. Results from the pharmacokinetics (PK) study support weekly dosing. In the first 24 hours following a MTD dose, hyperglycemia of grade 2 or 3 may occur. Clinical SD, pharmacokinetics, and FDG-PET data all support effective exposure and PI3K pathway inhibition.
| Targets |
PI3Kα (IC50 = 0.5 nM); PI3Kδ (IC50 = 0.7 nM); PI3Kβ (IC50 = 3.7 nM); PI3Kγ (IC50 = 6.4 nM); mTOR (IC50 = 45 nM)
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| ln Vitro |
BAY 80-6946 lowers pAKT levels in KPL4 cells and LPA-stimulated PC3 cells. BAY 80-6946 exhibits antiproliferative activity and induces apoptosis in a subset of human cancer cell lines with PIK3CA mutations and/or overexpression of HER2. [1] Combining HER2-targeted therapies with BAY 80-6946 inhibits growth more potently than either therapy when used independently, and it can improve cells' sensitivity to trastuzumab and lapatinib. [2]
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| ln Vivo |
BAY 80-6946 (6 mg/kg, i.v.) causes 100% complete tumor regression in rat KPL4 or HCT116 tumor xenograft models. BAY 80-6946 (14 mg/kg, i.v.) also inhibits tumor growth in nude mice with patient-derived luminal breast tumor models MAXF1398 and Lu7860 erlotinib-resistant NSCLC. [1]
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| Enzyme Assay |
The effect of BAY 80-6946 on PI3Kα, PI3Kβ, and PI3Kγ activity is measured by the inhibition of 33P incorporation into phosphatidylinositol (PI) in 384-well MaxiSorp® plates coated with 2 µg/well of PI and phosphatidylserine (PS) (1:1 molar ratio). In each PI3K isoform assay, 9 µL of reaction buffer (50 mM MOPSO, pH 7.0, 100 mM NaCl, 4 mM MgCl2, 0.1% BSA) containing 7.5 ng of His-tagged N-terminal truncated p110α or p110β protein, or 25 ng of purified human p110γ protein, is used. The reaction is started by adding 5 µL of a 40-µM ATP solution containing 20 µCi/mL [33>/sup>P]-ATP. After 2 hours incubation at room temperature, the reaction is terminated by addition of 5 µL of a 25-mM EDTA solution. The plates are washed and Ultima Gold™ scintillation cocktail (25 µL) is then added. The radioactivity incorporated into the immobilized PI substrate is determined with a BetaPlate Liquid Scintillation Counter.
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| Cell Assay |
The CellTiter-Glo® luminescent cell viability kit measures cell proliferation over a 72-hour period. Cells are briefly plated in distinct microtiter plates. The luminescence values in the t=0 hour plates are calculated after an overnight incubation at 37 °C. The cells are then incubated for 72 hours at 37°C after test substances have been added to the t=72 hour plates and diluted in growth medium. After a 10-minute reaction with CellTiter-Glo® solution, luminescence values are calculated using a Wallac 1420 Victor2TM 1420 multilabel HTS counter. By deducting the luminescence values in the t=0 hour plates from the corresponding values in the t=72 hour plates, the percentage inhibition of cell growth is calculated.
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| Animal Protocol |
Rats bearing KPL4 or HCT116 xenografts.
6 mg/kg i.v. |
| References |
| Molecular Formula |
C23H28N8O4
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|---|---|
| Molecular Weight |
480.5196
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| Exact Mass |
480.22335
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| Elemental Analysis |
C, 57.49; H, 5.87; N, 23.32; O, 13.32
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| CAS # |
1032568-63-0
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| Related CAS # |
Copanlisib dihydrochloride;1402152-13-9
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| Appearance |
white solid powder
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| SMILES |
COC1=C(C=CC2=C3NCCN3C(=NC(=O)C4=CN=C(N=C4)N)N=C21)OCCCN5CCOCC5
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| InChi Key |
MWYDSXOGIBMAET-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H28N8O4/c1-33-19-17(35-10-2-6-30-8-11-34-12-9-30)4-3-16-18(19)28-23(31-7-5-25-20(16)31)29-21(32)15-13-26-22(24)27-14-15/h3-4,13-14,25H,2,5-12H2,1H3,(H2,24,26,27)
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| Chemical Name |
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide
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| Synonyms |
Aliqopa;BAY 80-6946; BAY80-6946; BAY-80-6946; BAY806946; BAY-806946; BAY 806946
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~<1 mg/mL
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 20 mg/mL (41.62 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 10% Trifluoroacetic acid water solution: 1mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04750941 | Active Recruiting |
Drug: Copanlisib Other: Ketogenic Diet |
Follicular Lymphoma Endometrial Cancer |
Columbia University | February 10, 2022 | Phase 2 |
| NCT04431635 | Active Recruiting |
Drug: Copanlisib Drug: Nivolumab |
Indolent Lymphoma | AUniversity of Michigan Rogel Cancer Center |
June 15, 2020 | Phase 1 |
| NCT02465060 | Active Recruiting |
Drug: Afatinib Drug: Copanlisib |
Glioma Lymphoma |
National Cancer Institute (NCI) |
August 12, 2015 | Phase 2 |
| NCT05490771 | Active Recruiting |
Drug: Copanlisib Hydrochloride Procedure: Biopsy |
Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
June 20, 2018 | Phase 2 |
| NCT04462471 | Active Recruiting |
Drug: Vemurafenib Drug: Copanlisib |
Thyroid Cancer Thyroid Carcinoma |
Memorial Sloan Kettering Cancer Center |
June 26, 2020 | Phase 1 |
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