Identification

Name
Copanlisib
Accession Number
DB12483
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
BAY-80-6946 / BAY80-6946
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AliqopaInjection, powder, lyophilized, for solution15 mg/mLIntravenousBayer2017-09-14Not applicableUs
Categories
UNII
WI6V529FZ9
CAS number
1032568-63-0
Weight
Average: 480.529
Monoisotopic: 480.223351414
Chemical Formula
C23H28N8O4
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

Pharmacology

Indication

Indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.

Structured Indications
Not Available
Pharmacodynamics

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 [FDA 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 [FDA Label].

TargetActionsOrganism
APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
inhibitor
Human
APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
inhibitor
Human
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 [FDA 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 [FDA 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 [FDA 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 [FDA 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 [FDA Label].

Clearance

The geometric mean clearance is 17.9 (range: 7.3 to 51.4; SD: 8.5) L/hr [FDA Label].

Toxicity

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 [FDA Label].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Copanlisib can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Copanlisib can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Copanlisib can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Copanlisib can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Copanlisib can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Copanlisib can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Copanlisib can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Copanlisib can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe metabolism of Copanlisib can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Copanlisib can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Copanlisib can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Copanlisib can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Copanlisib can be increased when it is combined with Amsacrine.Approved
AprepitantThe serum concentration of Copanlisib can be increased when it is combined with Aprepitant.Approved, Investigational
AstemizoleThe serum concentration of Copanlisib can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe metabolism of Copanlisib can be decreased when combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Copanlisib can be increased when it is combined with Atenolol.Approved
AtomoxetineThe metabolism of Copanlisib can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Copanlisib can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Copanlisib can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Copanlisib can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Copanlisib can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Copanlisib can be increased when it is combined with Bepridil.Approved, Withdrawn
BiperidenThe serum concentration of Copanlisib can be increased when it is combined with Biperiden.Approved
BoceprevirThe metabolism of Copanlisib can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Copanlisib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Copanlisib can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Copanlisib can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Copanlisib can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Copanlisib can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Copanlisib can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Copanlisib can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Copanlisib can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Copanlisib can be increased when it is combined with Canagliflozin.Approved
Candesartan cilexetilThe serum concentration of Copanlisib can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Copanlisib can be increased when it is combined with Captopril.Approved
CarbamazepineThe metabolism of Copanlisib can be increased when combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Copanlisib can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Copanlisib can be increased when it is combined with Caspofungin.Approved
CeritinibThe serum concentration of Copanlisib can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Copanlisib can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Copanlisib can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Copanlisib can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Copanlisib can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Copanlisib can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Copanlisib can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Copanlisib can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Copanlisib can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Copanlisib can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Copanlisib can be increased when it is combined with Citalopram.Approved
ClarithromycinThe metabolism of Copanlisib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Copanlisib can be decreased when combined with Clemastine.Approved
ClofazimineThe serum concentration of Copanlisib can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Copanlisib can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Copanlisib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Copanlisib can be decreased when combined with Cobicistat.Approved
ColchicineThe serum concentration of Copanlisib can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Copanlisib can be increased when it is combined with Colforsin.Experimental
ConivaptanThe serum concentration of Copanlisib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Copanlisib can be decreased when combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Copanlisib can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe metabolism of Copanlisib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Copanlisib can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Copanlisib can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Copanlisib can be increased when it is combined with Dactinomycin.Approved
DarunavirThe metabolism of Copanlisib can be decreased when combined with Darunavir.Approved
DaunorubicinThe serum concentration of Copanlisib can be decreased when it is combined with Daunorubicin.Approved
DeferasiroxThe serum concentration of Copanlisib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Copanlisib can be decreased when combined with Delavirdine.Approved
DesipramineThe serum concentration of Copanlisib can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Copanlisib can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Copanlisib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Copanlisib can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Copanlisib can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Copanlisib can be decreased when it is combined with Digoxin.Approved
DihydroergotamineThe metabolism of Copanlisib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Copanlisib can be decreased when combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Copanlisib can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Copanlisib can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Copanlisib can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Copanlisib can be decreased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Copanlisib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Copanlisib can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe metabolism of Copanlisib can be decreased when combined with Dronedarone.Approved
ElbasvirThe serum concentration of Copanlisib can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Copanlisib can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Copanlisib can be increased when it is combined with Enalapril.Approved, Vet Approved
EnasidenibThe serum concentration of Copanlisib can be increased when it is combined with Enasidenib.Approved
EnzalutamideThe serum concentration of Copanlisib can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Copanlisib can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Copanlisib can be increased when it is combined with Ergotamine.Approved
ErythromycinThe metabolism of Copanlisib can be decreased when combined with Erythromycin.Approved, Vet Approved
EstramustineThe serum concentration of Copanlisib can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Copanlisib can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Copanlisib can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Copanlisib can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Copanlisib can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Copanlisib can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Copanlisib can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Copanlisib can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Copanlisib can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe metabolism of Copanlisib can be decreased when combined with Fluconazole.Approved
FluoxetineThe serum concentration of Copanlisib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Copanlisib can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Copanlisib can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Copanlisib can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe metabolism of Copanlisib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Copanlisib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Copanlisib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Copanlisib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Copanlisib can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Copanlisib can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Copanlisib can be increased when it is combined with Genistein.Investigational
GlecaprevirThe serum concentration of Copanlisib can be increased when it is combined with Glecaprevir.Approved
GlyburideThe serum concentration of Copanlisib can be increased when it is combined with Glyburide.Approved
GlycerinThe serum concentration of Copanlisib can be increased when it is combined with Glycerin.Approved, Investigational
Gramicidin DThe serum concentration of Copanlisib can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Copanlisib can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Copanlisib can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Copanlisib can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Copanlisib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Copanlisib can be decreased when combined with Imatinib.Approved
ImipramineThe serum concentration of Copanlisib can be increased when it is combined with Imipramine.Approved
IndinavirThe metabolism of Copanlisib can be decreased when combined with Indinavir.Approved
IndomethacinThe serum concentration of Copanlisib can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoniumThe metabolism of Copanlisib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Copanlisib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Copanlisib can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Copanlisib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Copanlisib can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Copanlisib can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe metabolism of Copanlisib can be decreased when combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Copanlisib can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Copanlisib can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Copanlisib can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Copanlisib can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Copanlisib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Copanlisib can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Copanlisib can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Copanlisib can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Copanlisib can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Copanlisib can be increased when it is combined with Loperamide.Approved
LopinavirThe metabolism of Copanlisib can be decreased when combined with Lopinavir.Approved
LoratadineThe serum concentration of Copanlisib can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Copanlisib can be increased when it is combined with Losartan.Approved
LovastatinThe metabolism of Copanlisib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Copanlisib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Copanlisib can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Copanlisib can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Copanlisib can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Copanlisib can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Copanlisib can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Copanlisib can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Copanlisib can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Copanlisib can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Copanlisib can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Copanlisib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Copanlisib can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Copanlisib can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Copanlisib can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Copanlisib can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Copanlisib can be decreased when it is combined with Mitoxantrone.Approved, Investigational
MorphineThe serum concentration of Copanlisib can be increased when it is combined with Morphine.Approved, Investigational
NaltrexoneThe serum concentration of Copanlisib can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Copanlisib can be increased when it is combined with Naringenin.Experimental
NefazodoneThe metabolism of Copanlisib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Copanlisib can be decreased when combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Copanlisib can be increased when it is combined with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Copanlisib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Copanlisib can be increased when combined with Nevirapine.Approved
NicardipineThe serum concentration of Copanlisib can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Copanlisib can be decreased when it is combined with Nifedipine.Approved
NilotinibThe metabolism of Copanlisib can be decreased when combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Copanlisib can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Copanlisib can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Copanlisib can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Copanlisib can be decreased when it is combined with Norethisterone.Approved
OlaparibThe metabolism of Copanlisib can be decreased when combined with Olaparib.Approved
OmeprazoleThe serum concentration of Copanlisib can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Copanlisib can be increased when it is combined with Osimertinib.Approved
P-NitrophenolThe serum concentration of Copanlisib can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Copanlisib can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Copanlisib can be increased when it is combined with Palbociclib.Approved
Palmitic AcidThe serum concentration of Copanlisib can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Copanlisib can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Copanlisib can be increased when it is combined with Paroxetine.Approved, Investigational
PentobarbitalThe metabolism of Copanlisib can be increased when combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Copanlisib can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe metabolism of Copanlisib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Copanlisib can be increased when combined with Phenytoin.Approved, Vet Approved
PibrentasvirThe serum concentration of Copanlisib can be increased when it is combined with Pibrentasvir.Approved
PimozideThe serum concentration of Copanlisib can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Copanlisib can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Copanlisib can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe metabolism of Copanlisib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Copanlisib can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Copanlisib can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Copanlisib can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe metabolism of Copanlisib can be increased when combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Copanlisib can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Copanlisib can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Copanlisib can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Copanlisib can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Copanlisib can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Copanlisib can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Copanlisib can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Copanlisib can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Copanlisib can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Copanlisib can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Copanlisib can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Copanlisib can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Copanlisib can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Copanlisib can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Copanlisib can be decreased when it is combined with Reserpine.Approved
RifabutinThe metabolism of Copanlisib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Copanlisib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Copanlisib can be increased when combined with Rifapentine.Approved
RilpivirineThe serum concentration of Copanlisib can be increased when it is combined with Rilpivirine.Approved
RitonavirThe metabolism of Copanlisib can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Copanlisib can be decreased when combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Copanlisib can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Copanlisib can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Copanlisib can be increased when it is combined with Sertraline.Approved
SildenafilThe metabolism of Copanlisib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Copanlisib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Copanlisib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Copanlisib can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Copanlisib can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Copanlisib can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Copanlisib can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Copanlisib can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Copanlisib can be increased when it is combined with Staurosporine.Experimental
StiripentolThe serum concentration of Copanlisib can be increased when it is combined with Stiripentol.Approved
StreptozocinThe serum concentration of Copanlisib can be decreased when it is combined with Streptozocin.Approved
SulfinpyrazoneThe serum concentration of Copanlisib can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe metabolism of Copanlisib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Copanlisib can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Copanlisib can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Copanlisib can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Copanlisib can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Copanlisib can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Copanlisib can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe metabolism of Copanlisib can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Copanlisib can be decreased when combined with Telithromycin.Approved
TelmisartanThe serum concentration of Copanlisib can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Copanlisib can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Copanlisib can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Copanlisib can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Copanlisib can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Copanlisib can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Copanlisib can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Copanlisib can be increased when it is combined with Ticagrelor.Approved
TiclopidineThe metabolism of Copanlisib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Copanlisib can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Copanlisib can be increased when it is combined with Tolvaptan.Approved
TrazodoneThe serum concentration of Copanlisib can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Copanlisib can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Copanlisib can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Copanlisib can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Copanlisib can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Copanlisib can be increased when it is combined with Troleandomycin.Approved
VelpatasvirThe serum concentration of Copanlisib can be increased when it is combined with Velpatasvir.Approved
VenlafaxineThe metabolism of Copanlisib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Copanlisib can be decreased when combined with Verapamil.Approved
VinblastineThe serum concentration of Copanlisib can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Copanlisib can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Copanlisib can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe metabolism of Copanlisib can be decreased when combined with Voriconazole.Approved, Investigational
VoxilaprevirThe serum concentration of Copanlisib can be increased when it is combined with Voxilaprevir.Approved
ZimelidineThe serum concentration of Copanlisib can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe metabolism of Copanlisib can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:27672108]
  2. FDA Press Announcements: FDA approves new treatment for adults with relapsed follicular lymphoma [Link]
External Links
ChemSpider
25069683
ChEMBL
CHEMBL3218576
HET
6E2
PDB Entries
5g2n
FDA label
Download (288 KB)
MSDS
Download (27.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherNon Hodgkin Lymphoma (NHL)1
1CompletedTreatmentNeoplasms5
1RecruitingOtherOncology, Medical1
1RecruitingTreatmentHER2 Positive Breast Cancers1
1, 2Not Yet RecruitingTreatmentEstrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Multifocal Breast Carcinoma / One to five years postmenopausal / Progesterone Receptor Positive / Stage I Breast Carcinoma / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage III Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
1, 2Not Yet RecruitingTreatmentMature T-Cell and NK-Cell Neoplasm1
1, 2RecruitingTreatmentCarcinoma, Squamous Cell of Head and Neck1
1, 2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentLymphoma, Diffuse Large-Cell1
2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentBiliary Carcinoma / Cholangiocarcinomas / Gall Bladder Carcinoma / Gastrointestinal Tumors1
2SuspendedTreatmentEndometrial Endometrioid Adenocarcinoma / Endometrial Mixed Adenocarcinoma / Endometrial Serous Adenocarcinoma / Endometrial Undifferentiated Carcinoma / Metastatic Endometrioid Adenocarcinoma / PIK3CA Gene Mutation / Recurrent Uterine Corpus Carcinoma1
2TerminatedTreatmentLymphoma, Mantle-Cell1
3Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentLymphoma,Non-Hodgkin1
3RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous15 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.231 mg/mLALOGPS
logP1.02ALOGPS
logP0.32ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)10.15ChemAxon
pKa (Strongest Basic)6.88ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area139.79 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity132.78 m3·mol-1ChemAxon
Polarizability51.76 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Quinazolinamine / Pyrimidinecarboxamide / Pyrimidine-5-carboxylic acid or derivatives / Anisole / Phenol ether / Alkyl aryl ether / Aminopyrimidine / Pyrimidine / Imidolactam / Morpholine
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
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
Human
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
Human
Pharmacological action
No
Actions
Substrate
General Function
Monooxygenase activity
Specific Function
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name
CYP3A43
Uniprot ID
Q9HB55
Uniprot Name
Cytochrome P450 3A43
Molecular Weight
57669.21 Da

Carriers

Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Inhibitor
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

Drug created on October 20, 2016 16:33 / Updated on September 16, 2017 00:46