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| 5mg |
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| 25mg |
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Purity: ≥98%
Copanlisib HCl (formerly BAY-806946; BAY 80-6946; Aliqopa), the hydrochloride salt of Copanlisib, is a pan-class I PI3K (phosphoinositide 3-kinase) inhibitor approved in 2017 for the treatment of relapsed follicular lymphoma. In cell-free assays, it inhibits PI3Kα/β/γ/δ with IC50 values of 0.5, 3.7, 6.4, and 0.7 nM, respectively. The FDA approved copanlisib in 2017 for the treatment of adults with relapsed follicular lymphoma. Phosphoinositide 3-kinase (PI3K) inhibitor BAY 80-6946 has potential anticancer properties and inhibits proliferation in HuCCT-1 (KRASG12D) and EGI-1 (KRASG12D) cell lines with IC50 values of 147 nM and 137 nM, respectively. The maximum tolerated dose (MTD) of BAY 80-6946 is generally well tolerated at 0.8 mg/kg. The results of pharmacokinetics (PK) 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); mTOP (IC50 = 45 nM)
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| ln Vitro |
In both KPL4 cells and LPA-stimulated PC3 cells, BAY 80-6946 reduces pAKT levels. BAY 80-6946 exhibits antiproliferative activity and induces apoptosis in a subset of human cancer cell lines that have PIK3CA mutations and/or overexpression of HER2. Combining HER2-targeted therapies with BAY 80-6946 inhibits growth more effectively than either therapy when used separately and can improve cells' sensitivity to trastuzumab and lapatinib.
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| ln Vivo |
Copanlisib (BAY 80-6946; 0.5-6 mg/kg; intravenous injection; every second day, every third day; for 60 days; athymic nude rats) treatment exhibits significant antitumor activity in the rat KPL4 tumor xenograft model[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) is used, containing either 25 ng of purified human p110γ protein or 7.5 ng of His-tagged N-terminally truncated p110α or p110β protein. Adding 5 µL liters of a 40-µM ATP solution with 20 µCi/mL [33>/sup>P]-ATP initiates the reaction. By adding 5 µL of a 25-mM EDTA solution, the reaction is stopped after 2 hours of incubation at room temperature. After washing the plates, Ultima GoldTM scintillation cocktail (25 µL) is added. With the help of a BetaPlate Liquid Scintillation Counter, the radioactivity incorporated into the immobilized PI substrate is identified.
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| Cell Assay |
The CellTiter-Glo® luminescent cell viability kit is used to calculate the rate of cell proliferation over a 72-hour period. In separate microtiter plates, cells are briefly plated. After an overnight incubation at 37 °C, the luminescence values in the t=0 hour plates are calculated. The cells are incubated in the t=72 hour plates for 72 hours at 37 °C after the addition of test substances that have been 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. Subtracting the luminescence values from the corresponding values in the t=72 hour plates, one can calculate the percentage inhibition of cell growth. Calculating the percentage of cell growth inhibition is done by comparing values between drug-treated cells and controls.
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| Animal Protocol |
Athymic nude rats injected with KPL4 tumor cells[1]
0.5 mg/kg, 1 mg/kg, 3 mg/kg or 6 mg/kg Intravenous injection; every second day, every third day; for 60 days |
| References |
| Molecular Formula |
C23H30CL2N8O4
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| Molecular Weight |
553.45
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| Exact Mass |
552.1767
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| Elemental Analysis |
C, 49.92; H, 5.46; Cl, 12.81; N, 20.25; O, 11.56
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| CAS # |
1402152-13-9
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| Related CAS # |
Copanlisib;1032568-63-0
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| Appearance |
Solid powder
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| SMILES |
O=C(C1=CN=C(N)N=C1)NC2=NC3=C(C=CC(OCCCN4CCOCC4)=C3OC)C5=NCCN25.[H]Cl.[H]Cl
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| InChi Key |
STGQPVQAAFJJFX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H28N8O4.2ClH/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;;/h3-4,13-14H,2,5-12H2,1H3,(H2,24,26,27)(H,28,29,32);2*1H
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| Chemical Name |
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| Synonyms |
BAY 80-6946; BAY80-6946; BAY-80-6946; BAY806946; BAY-806946; BAY 806946; Copanlisib HCl; Copanlisib dihydrochloride; Copanlisib; trade name Aliqopa
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (180.69 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 | 1.8068 mL | 9.0342 mL | 18.0685 mL | |
| 5 mM | 0.3614 mL | 1.8068 mL | 3.6137 mL | |
| 10 mM | 0.1807 mL | 0.9034 mL | 1.8068 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 |
| NCT03484819 | Active Recruiting |
Drug: Copanlisib Hydrochloride Biological: Nivolumab |
Recurrent Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma |
National Cancer Institute (NCI) |
October 19, 2018 | Phase 2 |
| NCT05490771 | Active Recruiting |
Procedure: Biopsy Drug: Copanlisib Hydrochloride |
Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
June 20, 2018 | Phase 2 |
| NCT04317105 | Active Recruiting |
Procedure: Biopsy Biological: Ipilimumab |
Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm |
National Cancer Institute (NCI) |
July 17, 2020 | Phase 1 Phase 2 |
| NCT02626455 | Active Recruiting |
Drug: Placebo Drug: Rituximab |
Lymphoma, Non-Hodgkin | Bayer | July 17, 2020 | Phase 3 |
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