Identification
- Summary
Copanlisib is a medication used to treat relapsed follicular lymphoma who have attempted at least two other treatments.
- Brand Names
- Aliqopa
- Generic Name
- Copanlisib
- DrugBank Accession Number
- DB12483
- Background
Copanlisib is a selective pan-Class I phosphoinositide 3-kinase (PI3K/Phosphatidylinositol-4,5-bisphosphate 3-kinase/phosphatidylinositide 3-kinase) inhibitor that was first developed by Bayer Healthcare Pharmaceuticals, Inc. The drug targets the enzyme that plays a role in regulating cell growth and survival. Copanlisib was granted accelerated approval on September 14, 2017 under the market name Aliqopa for the treatment of adult patients with relapsed follicular lymphoma and a treatment history of at least two prior systemic therapies. Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma that is caused by unregulated proliferation and growth of lymphocytes. The active ingredient in Aliquopa intravenous therapy is copanlisib dihydrochloride.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Copanlisib (DB12483)
- Weight
- Average: 480.529
Monoisotopic: 480.223351414 - Chemical Formula
- C23H28N8O4
- Synonyms
- Copanlisib
- External IDs
- BAY-80-6946
- BAY80-6946
Pharmacology
- Indication
Indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.
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- Contraindications & Blackbox Warnings
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Copanlisib has demonstrated potent anti-tumor and pro-apoptotic activity in various tumor cell lines and xenograft models 1. In clinical trials, 59 percent of patients receiving copanlisib achieved complete or partial shrinkage of their tumors after a median of 12.2 months 2. Higher systemic levels of copanlisib is associated with elevated plasma glucose levels.
- Mechanism of action
Follicular lymphoma is a B-cell lymphoma that is one of the most common type of non-Hodgkin lymphoma (NHL). It involves unregulated growth and proliferation of lymphocytes that eventually may travel to other organs including the lymph nodes, spleen, and the bone marrow, to form tumors. The phosphatidylinositol 3-kinase (PI3K)-mediated pathway is involved in promoting cell survival proliferation and differentiation however abberant activation of this pathway may lead to tumorigenesis 1. Copanlisib mediates an inhibitory action on p110α and p110δ isoforms of phosphatidylinositol-3-kinase (PI3K) expressed in malignant B cells. It induces tumor cell death via apoptosis and inhibits the proliferation of primary malignant B cell lines Label. Copanlisib inhibits several key cell-signaling pathways, including B-cell receptor (BCR) signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines Label.
Target Actions Organism APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitorHumans APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitorHumans - Absorption
The plasma levels of copanlisib increases in a dose-proportional manner with linear pharmacokinetic properties and no time dependency. Following a steady state exposure at 0.8 mg/kg, the mean peak plasma concentration (Cmax) of copanlisib is 463 ng/mL with the range of 105 to 1670 ng/mL Label.
- Volume of distribution
The in vitro mean blood-to-plasma ratio is 1.7 (range: 1.5 to 2.1). The geometric mean volume of distribution is 871 (range: 423 to 2150; SD: 479) L.
- Protein binding
The in vitro human plasma protein binding of copanlisib is 84.2%, with albumin being the main binding protein Label.
- Metabolism
Approximately >90% of copanlisib metabolism is mediated by CYP3A and less than 10% of the drug is metabolized by CYP1A1. The main detectable metabolite is M-1 that retains a comparable pharamcological activity to the parent drug against PI3Kα and PI3Kβ Label.
- Route of elimination
Copanlisib is excreted approximately 50% as unchanged compound and 50% as metabolites in humans. After a single intravenously-administered dose of 12mg radiolableled drug, approximately 64% of the dose is excreted in feces and 22% is excreted in urine within 20 to 34 days. Unchanged copanlisib represented approximately 30% of the administered dose in feces and 15% in urine. Metabolites resulting from CYP450-mediated oxidation metabolism accounted for 41% of the administered dose Label.
- Half-life
The geometric mean terminal elimination half-life of copanlisib is 39.1 (range: 14.6 to 82.4; SD: 15.0) hours Label.
- Clearance
The geometric mean clearance is 17.9 (range: 7.3 to 51.4; SD: 8.5) L/hr Label.
- Adverse Effects
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Copanlisib is not shown to exhibit mutagenetic actions in vitro or in vivo. In the repeat dose toxicity studies, copanlisib led to adverse events in the reproductive systems of male and female rats. The effects on male rats included adverse events on the testes (germinal epithelial degeneration, decreased weight, and/or tubular atrophy), epididymides (spermatic debris, decreased weight, and/or oligospermia/aspermia), and prostate (reduced secretion and/or decreased weight). Copanlisib induced adverse events on ovaries (hemorrhage, hemorrhagic cysts, and decreased weight), uterus (atrophy, decreased weight), vagina (mononuclear infiltration), and a dose-related reduction in the numbers of female rats in estrus Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Copanlisib can be increased when it is combined with Abametapir. Abatacept The metabolism of Copanlisib can be increased when combined with Abatacept. Abemaciclib Abemaciclib may decrease the excretion rate of Copanlisib which could result in a higher serum level. Abrocitinib The serum concentration of Copanlisib can be increased when it is combined with Abrocitinib. Acalabrutinib The metabolism of Copanlisib can be decreased when combined with Acalabrutinib. Acetaminophen The metabolism of Copanlisib can be increased when combined with Acetaminophen. Acetazolamide The metabolism of Copanlisib can be decreased when combined with Acetazolamide. Acyclovir The excretion of Acyclovir can be decreased when combined with Copanlisib. Adagrasib The serum concentration of Copanlisib can be increased when it is combined with Adagrasib. Adalimumab The metabolism of Copanlisib can be increased when combined with Adalimumab. 
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- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of copanlisib.
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of copanlisib and may reduce its serum concentration.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Copanlisib dihydrochloride 03ZI7RZ52O 1402152-13-9 STGQPVQAAFJJFX-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aliqopa Injection, powder, lyophilized, for solution 15 mg/1mL Intravenous Bayer HealthCare Pharmaceuticals Inc. 2017-09-14 Not applicable US 
Categories
- ATC Codes
- L01EM02 — Copanlisib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- MATE 2 Inhibitors
- MATE inhibitors
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Phosphatidylinositol-3-kinase (Pi3K) inhibitors
- Protein Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Quinazolinamines
- Alternative Parents
- Pyrimidinecarboxamides / Anisoles / Alkyl aryl ethers / Aminopyrimidines and derivatives / Morpholines / Imidolactams / Imidazolines / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives show 10 more
- Substituents
- 2-imidazoline / Alkyl aryl ether / Amidine / Amine / Amino acid or derivatives / Aminopyrimidine / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- WI6V529FZ9
- CAS number
- 1032568-63-0
- InChI Key
- PZBCKZWLPGJMAO-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 2-amino-N-{7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2H,3H-imidazo[1,2-c]quinazolin-5-yl}pyrimidine-5-carboxamide
- SMILES
- COC1=C(OCCCN2CCOCC2)C=CC2=C1N=C(NC(=O)C1=CN=C(N)N=C1)N1CCN=C21
References
- General References
- Patnaik A, Appleman LJ, Tolcher AW, Papadopoulos KP, Beeram M, Rasco DW, Weiss GJ, Sachdev JC, Chadha M, Fulk M, Ejadi S, Mountz JM, Lotze MT, Toledo FG, Chu E, Jeffers M, Pena C, Xia C, Reif S, Genvresse I, Ramanathan RK: First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas. Ann Oncol. 2016 Oct;27(10):1928-40. doi: 10.1093/annonc/mdw282. [Article]
- FDA Press Announcements: FDA approves new treatment for adults with relapsed follicular lymphoma [Link]
- FDA Approved Drug Products: Aliqopa (copanlisib) for intravenous injection [Link]
- External Links
- PubChem Compound
- 24989044
- PubChem Substance
- 347828721
- ChemSpider
- 25069683
- BindingDB
- 50204093
- 1945077
- ChEMBL
- CHEMBL3218576
- ZINC
- ZINC000068247389
- PDBe Ligand
- 6E2
- Wikipedia
- Copanlisib
- PDB Entries
- 5g2n
- FDA label
- Download (288 KB)
- MSDS
- Download (27.2 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 15 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9636344 No 2017-05-02 2032-03-29 US US8466283 No 2013-06-18 2029-10-22 US US7511041 No 2009-03-31 2024-05-13 US USRE46856 No 2018-05-22 2029-10-22 US US10383876 No 2019-08-20 2032-03-29 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.231 mg/mL ALOGPS logP 1.02 ALOGPS logP 0.32 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 10.15 Chemaxon pKa (Strongest Basic) 6.88 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 11 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 139.79 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 132.78 m3·mol-1 Chemaxon Polarizability 51.71 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein serine/threonine kinase activity
- Specific Function
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate...
- Gene Name
- PIK3CA
- Uniprot ID
- P42336
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- Molecular Weight
- 124283.025 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
- Specific Function
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by rec...
- Gene Name
- PIK3CD
- Uniprot ID
- O00329
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- Molecular Weight
- 119478.065 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- At clinically significant concentrations, this drug does not inhibit MATE2. However, in vitro studies have shown inhibition and supratherapeutic doses.
- General Function
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Kim RD, Alberts SR, Pena 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. [Article]
- Copanlisib FDA label [File]
Drug created at October 20, 2016 22:33 / Updated at February 21, 2021 18:53