WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 204570
CAS#: 1032568-63-0 (free base)
Description: Copanlisib also known as BAY 80-6946, is a potent phosphoinositide 3-kinase (PI3K) inhibitor. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents. Copanlisib was approved for the treatment of adult patients experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.
MedKoo Cat#: 204570
Name: Copanlisib free base
CAS#: 1032568-63-0 (free base)
Chemical Formula: C23H28N8O4
Exact Mass: 480.22335
Molecular Weight: 480.52
Elemental Analysis: C, 57.49; H, 5.87; N, 23.32; O, 13.32
Related CAS #: 1402152-13-9 (HCl) 1032568-63-0 (free base) 1402152-46-8 (HCl hydrate)
Synonym: BAY 80-6946; BAY80-6946; BAY-80-6946; BAY806946; BAY-806946; BAY 806946; Copanlisib free base
IUPAC/Chemical Name: 2-amino-N-(7-methoxy-8-(3-morpholinopropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyrimidine-5-carboxamide
InChi Key: PZBCKZWLPGJMAO-UHFFFAOYSA-N
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/h3-4,13-14H,2,5-12H2,1H3,(H2,24,26,27)(H,28,29,32)
SMILES Code: O=C(C1=CN=C(N)N=C1)NC2=NC3=C(C=CC(OCCCN4CCOCC4)=C3OC)C5=NCCN25.
Appearance: white solid powder
Purity: >95% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: BAY80-6946 does not have good solubility in common solvents. BAY80-6946 is soluble in 5% HCl, slightly soluble in DMSO, not soluble in water.
Shelf Life: >2 years if stored properly
Drug Formulation: Method 1: For in vitro studies, 5 mmol/L stock solution of BAY 80-6946 (in dimethyl sulfoxide with 10 mmol/L trifluoroacetic acid) was used - see Mol Cancer Ther. 2013 Nov;12(11):2319-30.
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 480.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548413/ PubMed PMID: 31643732.
2: Morschhauser F, Machiels JP, Salles G, Rottey S, Rule SA, Cunningham D, Peyrade F, Fruchart C, Arkenau HT, Genvresse I, Liu L, Köchert K, Shen K, Kneip C, Peña CE, Grevel J, Zhang J, Cisternas G, Reschke S, Granvil C, Awada A. On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors. Mol Cancer Ther. 2019 Oct 16. pii: molcanther.0466.2019. doi: 10.1158/1535-7163.MCT-19-0466. [Epub ahead of print] PubMed PMID: 31619463.
3: Ye L, Mayerle J, Ziesch A, Reiter FP, Gerbes AL, De Toni EN. The PI3K inhibitor copanlisib synergizes with sorafenib to induce cell death in hepatocellular carcinoma. Cell Death Discov. 2019 Apr 5;5:86. doi: 10.1038/s41420-019-0165-7. eCollection 2019. PubMed PMID: 30962952; PubMed Central PMCID: PMC6450909.
4: Eltantawy A, Vallejos X, Sebea E, Evans K. Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma. Ann Pharmacother. 2019 Sep;53(9):954-958. doi: 10.1177/1060028019833992. Epub 2019 Feb 27. PubMed PMID: 30813760.
5: Appukkuttan S, Duchesneau E, Zichlin ML, Bhak RH, Yaldo A, Gharibo M, Babajanyan S, Duh MS. A Budget Impact Analysis of the Introduction of Copanlisib for Treatment of Relapsed Follicular Lymphoma in the United States. J Manag Care Spec Pharm. 2019 Jan 4:1-12. doi: 10.18553/jmcp.2019.18259. [Epub ahead of print] PubMed PMID: 30608008.
6: Cheson BD, O'Brien S, Ewer MS, Goncalves MD, Farooki A, Lenz G, Yu A, Fisher RI, Zinzani PL, Dreyling M. Optimal Management of Adverse Events From Copanlisib in the Treatment of Patients With Non-Hodgkin Lymphomas. Clin Lymphoma Myeloma Leuk. 2019 Mar;19(3):135-141. doi: 10.1016/j.clml.2018.11.021. Epub 2018 Nov 29. PubMed PMID: 30584024; PubMed Central PMCID: PMC6642803.
7: Dittakavi S, Mullangi R. LC-ESI-MS/MS determination of copanlisib, a novel PI3K inhibitor, in mouse plasma and its application to a pharmacokinetic study in mice. Biomed Chromatogr. 2019 Apr;33(4):e4460. doi: 10.1002/bmc.4460. Epub 2019 Jan 7. PubMed PMID: 30536684.
8: Okabe S, Tanaka Y, Tauchi T, Ohyashiki K. Copanlisib, a novel phosphoinositide 3-kinase inhibitor, combined with carfilzomib inhibits multiple myeloma cell proliferation. Ann Hematol. 2019 Mar;98(3):723-733. doi: 10.1007/s00277-018-3547-7. Epub 2018 Nov 15. PubMed PMID: 30430191.
9: Krause G, Hassenrück F, Hallek M. Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib. Drug Des Devel Ther. 2018 Aug 21;12:2577-2590. doi: 10.2147/DDDT.S142406. eCollection 2018. Review. PubMed PMID: 30174412; PubMed Central PMCID: PMC6109662.
10: Mensah FA, Blaize JP, Bryan LJ. Spotlight on copanlisib and its potential in the treatment of relapsed/refractory follicular lymphoma: evidence to date. Onco Targets Ther. 2018 Aug 13;11:4817-4827. doi: 10.2147/OTT.S142264. eCollection 2018. Review. PubMed PMID: 30147333; PubMed Central PMCID: PMC6097514.
11: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500940/ PubMed PMID: 29999999.
12: Dreyling M. A closer look at copanlisib. Clin Adv Hematol Oncol. 2018 Jan;16(1):35-37. PubMed PMID: 29741503.
13: Copanlisib (Aliqopa) for relapsed follicular lymphoma. Med Lett Drugs Ther. 2018 Apr 23;60(1545):e74-e75. PubMed PMID: 29667951.
14: Kim RD, Alberts SR, Peña C, Genvresse I, Ajavon-Hartmann A, Xia C, Kelly A, Grilley-Olson JE. Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer. Br J Cancer. 2018 Feb 20;118(4):462-470. doi: 10.1038/bjc.2017.428. Epub 2018 Jan 18. PubMed PMID: 29348486; PubMed Central PMCID: PMC5830590.
15: Markham A. Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. Review. PubMed PMID: 29127587.
16: Copanlisib Produces Prolonged Responses in Lymphoma. Cancer Discov. 2017 Dec;7(12):OF2. doi: 10.1158/2159-8290.CD-NB2017-147. Epub 2017 Oct 25. PubMed PMID: 29070613.
17: Das M. Copanlisib in heavily pretreated indolent lymphoma. Lancet Oncol. 2017 Nov;18(11):e650. doi: 10.1016/S1470-2045(17)30783-0. Epub 2017 Oct 13. PubMed PMID: 29033198.
18: Dreyling M, Santoro A, Mollica L, Leppä S, Follows GA, Lenz G, Kim WS, Nagler A, Panayiotidis P, Demeter J, Özcan M, Kosinova M, Bouabdallah K, Morschhauser F, Stevens DA, Trevarthen D, Giurescu M, Cupit L, Liu L, Köchert K, Seidel H, Peña C, Yin S, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL. Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2017 Dec 10;35(35):3898-3905. doi: 10.1200/JCO.2017.75.4648. Epub 2017 Oct 4. Erratum in: J Clin Oncol. 2018 Feb 10;36(5):521. PubMed PMID: 28976790.
19: Gerisch M, Schwarz T, Lang D, Rohde G, Reif S, Genvresse I, Reschke S, van der Mey D, Granvil C. Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [(14)C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers. Cancer Chemother Pharmacol. 2017 Sep;80(3):535-544. doi: 10.1007/s00280-017-3383-9. Epub 2017 Jul 11. PubMed PMID: 28714036; PubMed Central PMCID: PMC5573760.
20: Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. doi: 10.1093/annonc/mdx289. PubMed PMID: 28633365; PubMed Central PMCID: PMC5834070.
BAY 80-6946 is a potent and highly selective reversible pan-Class I PI3K inhibitor with anti-tumor activity in a panel of preclinical models. A phase I dose escalation multicenter study showed that BAY 80-6946 was generally well tolerated through the MTD of 0.8 mg/kg. PK 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. (source: J Clin Oncol 29: 2011 (suppl; abstr 3035)
Tips for making stock solution
Due to its chemical nature, pure BAY80-6946 solid powder was found to have very low solubility in common organic solvents. This has been reported in the literature. User may use the following method as a reference when making stock solution: 2 mg BAY80-6946 is placed in a clear vial. To this vial, 10 µL 10% HCl is added. The vial is capped and shaken for a few seconds to allow HCl solution to wet the crystals of BAY80-6946. Then 90 µL water is added, and shaken for a few second, which will give a clear stock solution at 20 mg /mL. This solution can be further diluted using 0.5% HCl water solution.
This solution can be further diluted using 0.5% HCl water solution.
Pure BAY80-6946 has very low solubility, because of its chemical property, not because of the poor quality of our product. Molecule of BAY80-6946 contains several basic nitrogen atoms, after protonated by HCl, its solubility will be enhanced. For in vitro studies, 5 mmol/L stock solution of BAY 80-6946 (in dimethyl sulfoxide with 10 mmol/L trifluoroacetic acid) was used - see Mol Cancer Ther. 2013 Nov;12(11):2319-30.
