WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H204570
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.
Hodoodo Cat#: H204570
Name: Copanlisib free base
CAS#: 1032568-63-0 (free base)
Chemical Formula: C23H28N8O4
Exact Mass: 480.22
Molecular Weight: 480.520
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
More Info: 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.
| Biological target: | Copanlisib (BAY 80-6946) is a pan-class I PI3K inhibitor with IC50s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. |
| In vitro activity: | The antitumor activity of copanlisib, a novel pan-class-I PI3K inhibitor with predominant activity against p110α and p110δ isoforms, was evaulated. In vitro studies undertaken in one imatinib-sensitive (GIST-T1) and two imatinib-resistant (GIST-T1/670 and GIST430/654) GIST cell models showed that single-agent copanlisib effectively suppressed PI3K pathway activation leading to decreased cell viability and proliferation in both imatinib-sensitive and -resistant cells irrespective of the type of primary or secondary KIT mutations. Reference: Mol Cancer Ther. 2020 Jun;19(6):1289-1297. https://mct.aacrjournals.org/content/19/6/1289.long |
| In vivo activity: | The in vivo efficacy of copanlisib was determined using a xenograft model. Treatment of the NKS1 xenograft model with 25 mg/kg of copanlisib resulted in a significant decrease in tumour growth and reduced tumour weight (P < 0·01) (Fig4B, Figure S3). Consistent with the in vitro results, treatment of NKS1 with copanlisib also led to inhibition of AKT Ser473, EIF4EBP1 and STAT3 phosphorylation (Fig 4C), causing G0 /G1 cell cycle arrest and resulting in suppression of tumour cell growth. Interestingly, the cleaved PARP protein level was also significantly increased after copanlisib treatment, which was not observed in vitro. These data suggested that copanlisib might be a potent inhibitor for the treatment of NKTCL. Reference: Br J Haematol. 2020 May;189(4):731-744. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322801/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| 1M HCl | 100.0 | 208.11 | |
| DMSO | 0.5 | 1.04 |
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 |
| Formulation protocol: | 1. García-Valverde A, Rosell J, Serna G, Valverde C, Carles J, Nuciforo P, Fletcher JA, Arribas J, Politz O, Serrano C. Preclinical Activity of PI3K Inhibitor Copanlisib in Gastrointestinal Stromal Tumor. Mol Cancer Ther. 2020 Jun;19(6):1289-1297. doi: 10.1158/1535-7163.MCT-19-1069. Epub 2020 May 5. PMID: 32371592. 2. Huang D, Song TL, Nairismägi ML, Laurensia Y, Pang WL, Zhe DCM, Wong EKY, Wijaya GG, Tan J, Tan SH, Lim JQ, Chia BKH, Chan JY, Tang TPL, Somasundaram N, Cheng CL, Politz O, Liu N, Lim ST, Ong CK. Evaluation of the PIK3 pathway in peripheral T-cell lymphoma and NK/T-cell lymphoma. Br J Haematol. 2020 May;189(4):731-744. doi: 10.1111/bjh.16435. Epub 2020 Jan 31. PMID: 32004387; PMCID: PMC7322801. |
| In vitro protocol: | 1. García-Valverde A, Rosell J, Serna G, Valverde C, Carles J, Nuciforo P, Fletcher JA, Arribas J, Politz O, Serrano C. Preclinical Activity of PI3K Inhibitor Copanlisib in Gastrointestinal Stromal Tumor. Mol Cancer Ther. 2020 Jun;19(6):1289-1297. doi: 10.1158/1535-7163.MCT-19-1069. Epub 2020 May 5. PMID: 32371592. |
| In vivo protocol: | 1. Huang D, Song TL, Nairismägi ML, Laurensia Y, Pang WL, Zhe DCM, Wong EKY, Wijaya GG, Tan J, Tan SH, Lim JQ, Chia BKH, Chan JY, Tang TPL, Somasundaram N, Cheng CL, Politz O, Liu N, Lim ST, Ong CK. Evaluation of the PIK3 pathway in peripheral T-cell lymphoma and NK/T-cell lymphoma. Br J Haematol. 2020 May;189(4):731-744. doi: 10.1111/bjh.16435. Epub 2020 Jan 31. PMID: 32004387; PMCID: PMC7322801. |
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