Copanlisib
Explore a selection of our essential drug information below, or:
Identification
- Summary
Copanlisib is a PI3K inhibitor used to treat relapsed follicular lymphoma in adults.
- Brand Names
- Aliqopa
- Generic Name
- Copanlisib
- DrugBank Accession Number
- DB12483
- Background
Copanlisib is a selective pan-Class I phosphoinositide 3-kinase (PI3K) inhibitor with preferential activity against the alpha and delta isoforms. PI3K, a lipid kinase that activates downstream signalling pathways involved in cell survival and growth, that exists in different isoforms and is often overexpressed in hematological malignancies.2 Copanlisib was granted accelerated approval by the FDA in September 2017 for the treatment of follicular lymphoma.1
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 480.529
Monoisotopic: 480.223351414 - Chemical Formula
- C23H28N8O4
- Synonyms
- 2-AMINO-N-(7-METHOXY-8-(3-(MORPHOLIN-4-YL)PROPOXY)-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-5-YL(PYRIMIDINE-5-CARBOXAMIDE
- 2-AMINO-N-(7-METHOXY-8-(3-MORPHOLIN-4-YLPROPOXY)-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-5-YL)PYRIMIDINE-5-CARBOXAMIDE
- 5-PYRIMIDINECARBOXAMIDE, 2-AMINO-N-(2,3-DIHYDRO-7-METHOXY-8-(3-(4-MORPHOLINYL)PROPOXY)IMIDAZO(1,2-C)QUINAZOLIN-5-YL)-
- Copanlisib
- External IDs
- BAY 80-6946
- BAY-80-6946
- BAY80-6946
Pharmacology
- Indication
Copanlisib is indicated for the treatment of adults with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. This indication was granted under accelerated approval; thus, continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Relapsed follicular lymphoma •••••••••••• ••••• •• ••••• ••• ••••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Copanlisib is a kinase inhibitor with anti-tumour and pro-apoptotic activity in various tumour cell lines and xenograft models. Copanlisib causes an elevation in plasma glucose levels.5
- Mechanism of action
Phosphatidylinositol-3-kinase (PI3K) signalling pathway is implicated in cell proliferation and survival, as well as resistance to chemotherapeutic agents. PI3K isoforms are often overexpressed in B-cell malignancies, including follicular lymphoma.2 Copanlisib is a class I PI3K inhibitor with preferential activity against PI3K-α and PI3K-δ isoforms expressed in malignant B cells. It binds with IC50 values of 0.5, 3.7, 6.4, and 0.7 nmol/L against class I PI3K-α, β, γ, and δ isoforms, respectively.1 Copanlisibinduces tumour cell death by apoptosis, blocks cell cycle progression, and inhibits the proliferation of primary malignant B cell lines. Copanlisib inhibits several key cell signalling pathways, including B-cell receptor (BCR) signalling, CXCR12-mediated chemotaxis of malignant B cells, and NFκB signalling in lymphoma cell lines.1,5
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 UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform inhibitorHumans UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform inhibitorHumans - Absorption
The area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of copanlisib increase dose-proportionally over 5 to 93 mg (0.08 to 1.55 times the approved recommended dose) absolute dose range and exhibit linear pharmacokinetics (PK). There is no time-dependency and no accumulation in the pharmacokinetics of copanlisib. The geometric mean (range) steady state copanlisib exposure at 0.8 mg/kg (approximately the approved recommended dose of 60 mg) are 463 (range: 105 to 1670; SD: 584) ng/mL for Cmax and 1570 (range: 536 to 3410; SD: 338) ng x hr/mL for AUC0-25h.5
- Volume of distribution
The geometric mean volume of distribution is 871 (range: 423 to 2150; SD: 479) L.5
- Protein binding
Copanlisib is 84.2% bound to plasma proteins, mainly to serum albumin. The in vitro mean blood-to-plasma ratio is 1.7, with a range from 1.5 to 2.1.5
- Metabolism
Copanlisib is primarily metabolized by CYP3A (>90%) and to a lesser extent, CYP1A1 (<10%).3,5 The M1 metabolite accounts for 5% of total radioactivity in plasma and has a pharmacological activity that is comparable to that of the parent compound.3,5
Hover over products below to view reaction partners
- Route of elimination
In humans, approximately half of copanlisib is excreted as unchanged parent compound and the other half is excreted as metabolites. Following a single intravenous dose of 12 mg (0.2 times the recommended approved dose) radiolabeled copanlisib, approximately 64% of the administered dose was recovered in feces and 22% 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 accounted for 41% of the administered dose.5
- Half-life
The geometric mean terminal elimination half-life of copanlisib is 39.1 (range: 14.6 to 82.4; SD: 15.0) hours.5
- Clearance
The geometric mean clearance is 17.9 (range: 7.3 to 51.4; SD: 8.5) L/hr.5
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The LD50 of copanlisib dihydrochloride in male and female rats after a single intravenous dose administration was >23.0 mg/kg, which corresponds to 20.0 mg/kg copanlisib.6 There is no information on copanlisib overdose.
- 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. Acalabrutinib The metabolism of Copanlisib can be decreased when combined with Acalabrutinib. Acetaminophen The metabolism of Copanlisib can be increased when combined with Acetaminophen. - Food Interactions
- Avoid grapefruit products. Grapefruit strongly inhibits CYP3A metabolism, which may increase the serum concentration of copanlisib.
- Avoid St. John's Wort. This herb strongly 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 Copanlisib dihydrochloride hydrate W421JK3CPA 1402152-46-8 PRZNRMHJLYLVBJ-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
- Markham A: Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. [Article]
- 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. [Article]
- 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. [Article]
- FDA Press Announcements: FDA approves new treatment for adults with relapsed follicular lymphoma [Link]
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- EMA: Aliqopa (copanlisib) withdrawal assessment report [Link]
- External Links
- PubChem Compound
- 24989044
- PubChem Substance
- 347828721
- ChemSpider
- 25069683
- BindingDB
- 50204093
- 1945077
- ChEBI
- 173077
- ChEMBL
- CHEMBL3218576
- ZINC
- ZINC000068247389
- PDBe Ligand
- 6E2
- Wikipedia
- Copanlisib
- PDB Entries
- 5g2n
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Relapsed or Refractory Indolent Non-Hodgkin Lymphoma 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Cancer 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Non-Hodgkin's Lymphoma (NHL) 1 somestatus stop reason just information to hide 3 Completed Treatment Non-Hodgkin's Lymphoma (NHL) 1 somestatus stop reason just information to hide 3 Terminated Treatment Non-Hodgkin's Lymphoma (NHL) 1 somestatus stop reason just information to hide
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 splash10-001i-0300900000-bae1d15bd596281ff7ba Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-056r-0007900000-857ba35577042f590c14 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0104900000-7f9b89d528c93d2331a8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0401900000-2ae9b9abb943a2260cee Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0uei-2503900000-97de1a0645cb64d04cd7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-052r-2319300000-780a15f71bde0cb1ed99 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 232.6020052 predictedDarkChem Lite v0.1.0 [M-H]- 204.10176 predictedDeepCCS 1.0 (2019) [M+H]+ 232.0984052 predictedDarkChem Lite v0.1.0 [M+H]+ 206.45975 predictedDeepCCS 1.0 (2019) [M+Na]+ 233.6617052 predictedDarkChem Lite v0.1.0 [M+Na]+ 212.5529 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CA
- Uniprot ID
- P42336
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- Molecular Weight
- 124283.025 Da
References
- 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. [Article]
- Markham A: Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. [Article]
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:9235916). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CD
- Uniprot ID
- O00329
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- Molecular Weight
- 119478.065 Da
References
- 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. [Article]
- Markham A: Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. [Article]
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Has also a protein kinase activity showing autophosphorylation (PubMed:12502714)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CB
- Uniprot ID
- P42338
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
- Molecular Weight
- 122761.225 Da
References
- Markham A: Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CG
- Uniprot ID
- P48736
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Molecular Weight
- 126452.625 Da
References
- Markham A: Copanlisib: First Global Approval. Drugs. 2017 Dec;77(18):2057-2062. doi: 10.1007/s40265-017-0838-6. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- all-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- 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
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
- Specific Function
- antiporter activity
- 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]
- FDA Approved Drug Products: ALIQOPA (copanlisib) for injection, for intravenous use (September 2023) [Link]
- Copanlisib FDA label [File]
Drug created at October 20, 2016 22:33 / Updated at October 03, 2024 04:32