Copanlisib HCl | CAS#1402152-13-9 | PI3K inhibitor

MedKoo Cat#: 206945 | Name: Copanlisib HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Copanlisib HCl

CAS#1402152-13-9 (HCl)

Theoretical Analysis

MedKoo Cat#: 206945

Name: Copanlisib HCl

CAS#: 1402152-13-9 (HCl)

Chemical Formula: C23H30Cl2N8O4

Exact Mass: 552.1767

Molecular Weight: 553.45

Elemental Analysis: C, 49.92; H, 5.46; Cl, 12.81; N, 20.25; O, 11.56

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 380.00	Ready to ship
100mg	USD 700.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

1402152-13-9 (HCl) 1032568-63-0 (free base) 1402152-46-8 (HCl hydrate)

Synonym

Copanlisib HCl; Copanlisib dihydrochloride; BAY 80-6946; BAY80-6946; BAY-80-6946; BAY806946; BAY-806946; BAY 806946; Copanlisib; trade name Aliqopa.

IUPAC/Chemical Name

5-Pyrimidinecarboxamide, 2-amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, hydrochloride (1:2)

InChi Key

STGQPVQAAFJJFX-UHFFFAOYSA-N

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

SMILES Code

O=C(C1=CN=C(N)N=C1)NC2=NC3=C(C=CC(OCCCN4CCOCC4)=C3OC)C5=NCCN25.[H]Cl.[H]Cl

Appearance

Solid powder

Purity

>98% (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

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S8S05C02

QC Data

View QC data: current batch, Lot#S8S05C02

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Copanlisib (BAY 80-6946) is a potent, selective and ATP-competitive 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:

BAY 80-6946 potently inhibited the catalytic activity of the class I PI3Kα, β, γ, and δ isoforms with IC50 values of 0.5, 3.7, 6.4, and 0.7 nmol/L, respectively. It showed significantly weaker activity against mTOR with an IC50 of 45 nmol/L. In contrast, 1 μmol/L BAY 80-6946 did not inhibit PI4K-II, PIP4-5K, PIP5-4K, or an additional 220 kinases in the Millipore kinase panel (inhibition <30%), indicating that BAY 80-6946 is a specific PI3K inhibitor with more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. To further evaluate the selectivity of BAY 80-6946 against PI3K versus mTOR kinase, rat ELT3 cells, which exhibit a PI3K-independent activation of mTORC1 due to TCS2 deficiency, were used. Complete inhibition of PI3K-mediated AKT phosphorylation was clearly shown at a concentration of 5 nmol/L (Fig. 1B), whereas BAY 80-6946 showed only a minor reduction of PI3K-independent mTORC1-mediated phosphorylation of S70S6K levels and no effect at all on p-4E-BP1 at a concentration of 500 nmol/L (Fig. 1C). Reference: Mol Cancer Ther. 2013 Nov;12(11):2319-30. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=24170767

In vivo activity:

BAY 80-6946 is highly efficacious in rat and mouse tumor xenograft models following intravenous administration. BAY 80-6946 was well tolerated at all doses and schedules tested in the studies described here without producing any lethality. The maximum-tolerated dose (MTD) in rats was defined as 6 mg/kg. At the MTD, a maximum mean body weight loss of 6% to 10% occurred during the first few days of dosing and then consistently returned to the normal range by the end of the dosing period. The MTD in mice was more than 14 mg/kg with a every second day dosing schedule. BAY 80-6946 was highly efficacious in a variety of human tumor xenograft models derived from different tumor indications that exhibit an activated PI3K pathway. The drug displayed robust antitumor activity in the rat KPL4 tumor xenograft model, which is an estrogen-independent HER2-positive breast carcinoma that carries a somatic PIK3CA mutation. BAY 80-6946 was administered at 0.5 to 6 mg/kg i.v. every second day for a total of five doses starting on day 14, following tumor cell implantation. On day 25, 3 days after the last dose, TGI rates of 77%, 84%, 99%, and 100% were observed with BAY 80-6946 at doses of 0.5, 1, 3, and 6 mg/kg, respectively (Fig. 5A). Complete tumor regression was shown in 10 of 10 rats in the 3 and 6 mg/kg groups, and all rats remained tumor free at the termination of the study on day 73. Tumor growth delays more than 25 days were observed in the 0.5 and 1 mg/kg dose groups. Reference: Mol Cancer Ther. 2013 Nov;12(11):2319-30. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=24170767

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	2.08
	Water	0.7	1.39

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 553.45 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. Liu N, Rowley BR, Bull CO, Schneider C, Haegebarth A, Schatz CA, Fracasso PR, Wilkie DP, Hentemann M, Wilhelm SM, Scott WJ, Mumberg D, Ziegelbauer K. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models. Mol Cancer Ther. 2013 Nov;12(11):2319-30. doi: 10.1158/1535-7163.MCT-12-0993-T. Epub 2013 Oct 29. PMID: 24170767. 2. Schneider P, Schön M, Pletz N, Seitz CS, Liu N, Ziegelbauer K, Zachmann K, Emmert S, Schön MP. The novel PI3 kinase inhibitor, BAY 80-6946, impairs melanoma growth in vivo and in vitro. Exp Dermatol. 2014 Aug;23(8):579-84. doi: 10.1111/exd.12470. PMID: 24942196.

In vitro protocol:

In vivo protocol:

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.