U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C23H28N8O4
Molecular Weight 480.5196
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of COPANLISIB

SMILES

COC1=C(OCCCN2CCOCC2)C=CC3=C1N=C(NC(=O)C4=CN=C(N)N=C4)N5CCN=C35

InChI

InChIKey=PZBCKZWLPGJMAO-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
Molecular Formula C23H28N8O4
Molecular Weight 480.5196
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27310202 https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=653981 http://www.selleckchem.com/products/bay80-6946.html

Copanlisib, developed by Bayer, is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents. Copanlisib is currently under Phase II/III clinical trials for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia.

Originator

Approval Year

2017
422
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 3.7 nM [IC50]
Inhibitor
8297
 0.7 nM [IC50]
Inhibitor
8297
 0.5 nM [IC50]
Inhibitor
8297
 6.4 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
ALIQOPA

Approved Use

ALIQOPA is indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Launch Date

2017
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
463 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
60 mg 1 times / week steady-state, intravenous
dose: 60 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
447 μg/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27915408
0.8 mg/kg 1 times / week multiple, intravenous
dose: 0.8 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1570 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
60 mg 1 times / week steady-state, intravenous
dose: 60 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1280 μg × h/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27915408
0.8 mg/kg 1 times / week multiple, intravenous
dose: 0.8 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
39.1 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
60 mg 1 times / week steady-state, intravenous
dose: 60 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
35.6 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27915408
0.8 mg/kg 1 times / week multiple, intravenous
dose: 0.8 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
COPANLISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increased (grade 3, 1 patient)
Aspartate aminotransferase increased (grade 4, 1 patient)
Acidosis lactic (grade 4, 1 patient)
Anion gap (grade 4, 1 patient)
Ketonaemia (grade 4, 1 patient)
Left ventricular systolic dysfunction (grade 3, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Disc. AE: Hyperglycemia, Neutropenia...
AEs leading to
discontinuation/dose reduction:
Hyperglycemia (7%)
Neutropenia (5%)
Hypertension (5%)
Pneumonitis (2%)
Hyperglycemia (2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Disc. AE: Thrombocytopenia, Neutropenia...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (3%)
Neutropenia (1.8%)
Anemia (1.2%)
Nausea (1.2%)
Fatigue (2.4%)
Hypercalcemia (1.2%)
Acute kidney injury (1.6%)
Pneumonitis (3.6%)
Febrile neutropenia (1.8%)
Diarrhea (2.4%)
Pyrexia (5.4%)
Sepsis (1.8%)
Hyperglycemia (4.8%)
Pneumonitis (6%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
AEs

AEs

AESignificanceDosePopulation
Alanine aminotransferase increased grade 3, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Left ventricular systolic dysfunction grade 3, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Acidosis lactic grade 4, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Anion gap grade 4, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Aspartate aminotransferase increased grade 4, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Ketonaemia grade 4, 1 patient
DLT, Disc. AE
1.2 mg/kg 3 times / month steady, intravenous
Highest studied dose
Dose: 1.2 mg/kg, 3 times / month
Route: intravenous
Route: steady
Dose: 1.2 mg/kg, 3 times / month
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
unhealthy, 62 years (range: 35–86 years)
n = 3
Health Status: unhealthy
Age Group: 62 years (range: 35–86 years)
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/27672108
Hyperglycemia 2%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Pneumonitis 2%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Hypertension 5%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Neutropenia 5%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Hyperglycemia 7%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
Anemia 1.2%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Hypercalcemia 1.2%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Nausea 1.2%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Acute kidney injury 1.6%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Febrile neutropenia 1.8%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Neutropenia 1.8%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Sepsis 1.8%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Diarrhea 2.4%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Fatigue 2.4%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Thrombocytopenia 3%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Pneumonitis 3.6%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Hyperglycemia 4.8%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Pyrexia 5.4%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Pneumonitis 6%
Disc. AE
60 mg 3 times / month steady, intravenous
Recommended|MTD
Dose: 60 mg, 3 times / month
Route: intravenous
Route: steady
Dose: 60 mg, 3 times / month
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
unhealthy, adult
n = 168
Health Status: unhealthy
Condition: hematologic malignancies
Age Group: adult
Sex: M+F
Population Size: 168
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf
Page: зю 99
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882

UGT
35

MRP2
383

BSEP
402

OATP1B1
788

OATP1B3
706

OAT1
599

OAT3
642

OCT1
512

OCT2
647

P-gp
1461

BCRP
699

MATE1
306

MATE2
263
CYP3A
191

CYP3A4/5
85

CYP1A1
349
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BSEP
403
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
MRP2
475
 no
OAT1
603
 no
OAT3
644
 no
OATP1B1
803
 no
OATP1B3
715
 no
OCT1
543
 no
OCT2
648
 no
UGT
59
 no
MATE2
263
 yes [IC50 0.09 uM]
MATE1
308
 yes [IC50 10.8 uM]
BCRP
773
 yes [IC50 11.5 uM]
P-gp
1650
 yes [IC50 7 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A1
349
 yes
CYP3A4/5
85
 yes
CYP3A
191
 yes
yes (co-administration study)
Comment: ole, a strong CYP3A inhibitor which is also with inhibitory activity against human transporter P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), administered at a dose of 200 mg once daily for 10 days increased the mean AUC of a single IV dose of 60 mg ALIQOPA 53% with no effect on Cmax in patients with cancer
Page: 65.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA0039IF
https://www.aablocks.com/goods/Goods/detail?id=AA0039IF
AK Scientific, Inc. (AKSCI)
2253AH
http://www.aksci.com/item_detail.php?cat=2253AH
Aaron Chemicals
AR003AA7
http://www.aaronchem.com/1032568-63-0
AbMole Bioscience
M2436
http://www.abmole.com/products/bay-80-6946.html
Achemtek
0102-013863
http://www.achemtek.com/1032568-63-0
Adooq BioScience
A11766
https://www.adooq.com/bay-80-6946.html
Alsachim
4526
http://www.alsachim.com/product-C5867-glo.bal-view.html
Ambeed
A199526
https://www.ambeed.com/products/1032568-63-0.html
Ambinter
Amb22395971
http://www.ambinter.com/reference/22395971
Angel Pharmatech
AG-11182
http://www.angelpharmatech.com/1032568-63-0.html
Angene
AGN-PC-0WAJFZ
http://www.angenechemical.com/productshow/AGN-PC-0WAJFZ.html
ApexBio Technology
B2178
http://www.apexbt.com/bay-80-6946-copanlisib.html
Ark Pharm
AK172384
http://www.arkpharminc.com/products/1032568-63-0.html
Ark Pharma Scientific Limited
A-0609
http://www.arkpharmtech.com/product/32560.html
Aurora Fine Chemicals LLC
A24.109.961
http://online.aurorafinechemicals.com/info?ID=A24.109.961
Aurora Fine Chemicals LLC
K16.667.035
http://online.aurorafinechemicals.com/info?ID=K16.667.035
Aurum Pharmatech LLC
Q-4031
http://www.Aurumpharmatech.com/Product/ProductDetails/Q_4031
BioChemPartner
BCP04754
http://www.biochempartner.com/1032568-63-0-BCP04754
BioCrick
BCC4986
http://www.biocrick.com/BAY-80-6946-Copanlisib-BCC4986.html
CSNpharm
CSN15713
https://www.csnpharm.com/products/copanlisib.html
Chem Scene
CS-0741
http://www.chemscene.com/1032568-63-0.html
ChemShuttle
139014
http://www.chemshuttle.com/catalogsearch/result/?q=1032568-63-0&cat=
Chemenu
CM105548
http://www.chemenu.com/products/CM105548
Chemspace
CSSB00016994381
https://chem-space.com/CSSB00016994381
Clearsynth
CS-EK-01306
https://www.clearsynth.com/en/CSEK01306.html
DC Chemicals
DC9591
http://www.dcchemicals.com/product_show-BAY_80_6946.html
Excenen
EX-A2005
https://www.excenen.com/searchresultlist.php?id=1032568-63-0
Hefei Hirisun Pharmatech Co., Ltd
HR130780
http://www.hirisunpharm.com/1032568-63-0.html
Lab Network
LN01273450
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01273450
Lan Pharmatech
LAN-B38840
http://www.lanpharmatech.com/product-9?_keywords=LAN-B38840
MedChem Express
HY-15346
https://www.medchemexpress.com/BAY-80-6946.html
MolPort
MolPort-035-395-726
https://www.molport.com/shop/molecule-link/MolPort-035-395-726
MolPort
MolPort-046-594-376
https://www.molport.com/shop/molecule-link/MolPort-046-594-376
MuseChem
I000193
https://www.musechem.com/product/I000193.html
Selleck Chemicals
S2802
http://www.selleckchem.com/products/bay80-6946.html
Sinfoo Biotech
S061849
http://www.sinfoobiotech.com/product/1065267
Smolecule
S001528
http://www.smolecule.com/products/s001528
Smolecule
S548994
http://www.smolecule.com/products/s548994
Synblock Inc
PB22956
http://www.synblock.com/product/1032568-63-0.html
THE BioTek
bt-253069
https://www.thebiotek.com/product/inhibitors/bt-253069
THE BioTek
bt-287270
https://www.thebiotek.com/product/inhibitors/bt-287270
abcr GmbH
AB457959
http://www.abcr.de/shop/en/AB457959
eNovation Chemicals
D498912
https://www.enovationchem.com/ProductDetails.asp?ProductID=D498912
eNovation Chemicals
K31303
https://www.enovationchem.com/ProductDetails.asp?ProductID=K31303
eNovation Chemicals
Y0974317
https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974317
PubMed

PubMed

TitleDatePubMed
BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models.
2013 Nov
Preliminary results of a phase II study of single agent Bay 80-6946, a Novel PI3K inhibitor, in patients with relapsed/refractory, indolent or aggressive lymphoma.
2014 Feb
Patents

Patents

08466283
3
20110083984
3

Sample Use Guides

In Vivo Use Guide
60 mg in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle
Route of Administration: Oral
In Vitro Use Guide
Several breast cancer, endometrial cancer, and hematologic tumor cell lines were particularly sensitive to Copanlisib, with IC50 values less than 10nmol/L
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:26:49 GMT 2023
Edited
by admin
on Fri Dec 15 17:26:49 GMT 2023
Record UNII
WI6V529FZ9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
COPANLISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
2-AMINO-N-(7-METHOXY-8-(3-(MORPHOLIN-4-YL)PROPOXY)-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-5-YL(PYRIMIDINE-5-CARBOXAMIDE
Common Name English
COPANLISIB [MI]
Common Name English
BAY-80-6946
Code English
2-AMINO-N-(7-METHOXY-8-(3-MORPHOLIN-4-YLPROPOXY)-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-5-YL)PYRIMIDINE-5-CARBOXAMIDE
Systematic Name English
BAY80-6946
Code English
copanlisib [INN]
Common Name English
5-PYRIMIDINECARBOXAMIDE, 2-AMINO-N-(2,3-DIHYDRO-7-METHOXY-8-(3-(4-MORPHOLINYL)PROPOXY)IMIDAZO(1,2-C)QUINAZOLIN-5-YL)-
Systematic Name English
BAY 80-6946
Code English
COPANLISIB [USAN]
Common Name English
Copanlisib [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 463314
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
WHO-ATC L01XX61
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 811321
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 552416
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
NCI_THESAURUS C2152
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 811421
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 552616
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
NDF-RT N0000175605
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
FDA ORPHAN DRUG 552516
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
EU-Orphan Drug EU/3/18/2064
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
Code System Code Type Description
SMS_ID
100000170809
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
NCI_THESAURUS
C96796
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
PUBCHEM
24989044
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
MERCK INDEX
m12036
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
WIKIPEDIA
Copanlisib
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
EVMPD
SUB184952
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
RXCUI
1945077
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
DRUG CENTRAL
5256
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
ChEMBL
CHEMBL3218576
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
FDA UNII
WI6V529FZ9
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
CAS
1032568-63-0
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
DAILYMED
WI6V529FZ9
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
LACTMED
Copanlisib
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
USAN
CD-71
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
INN
9726
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
DRUG BANK
DB12483
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
CHEBI
173077
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID00145728
Created by admin on Fri Dec 15 17:26:49 GMT 2023 , Edited by admin on Fri Dec 15 17:26:49 GMT 2023
PRIMARY
Related Record Type Details
Structure of COPANLISIB HYDROCHLORIDE HYDRATE
SALT/SOLVATE -> PARENT
CYTOCHROME P450 1A1
METABOLIC ENZYME -> SUBSTRATE
MINOR
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT BETA ISOFORM
TARGET -> INHIBITOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
90% OF METABOLISM
MAJOR
Structure of COPANLISIB HYDROCHLORIDE
SALT/SOLVATE -> PARENT
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM
TARGET -> INHIBITOR
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM
TARGET -> INHIBITOR
MATE-2
TRANSPORTER -> INHIBITOR
IC50
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT ALPHA ISOFORM
TARGET -> INHIBITOR
Related Record Type Details
Structure of 2-AMINO-N-(2,3-DIHYDRO-8-HYDROXY-7-METHOXYIMIDAZO(1,2-C)QUINAZOLIN-5-YL)-5-PYRIMIDINECARBOXAMIDE
METABOLITE -> PARENT
(DEALKYLATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; URINE
Structure of 2-AMINO-N-(8-(3-(FORMYL(2-HYDROXYETHYL)AMINO)PROPOXY)-2,3-DIHYDRO-7-METHOXYIMIDAZO(1,2-C)QUINAZOLIN-5-YL)-5-PYRIMIDINECARBOXAMIDE
METABOLITE -> PARENT
(DEALKYLATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; URINE
Structure of 2-AMINO-N-(2,3-DIHYDRO-8-(3-((2-HYDROXYETHYL)AMINO)PROPOXY)-7-METHOXYIMIDAZO(1,2-C)QUINAZOLIN-5-YL)-5-PYRIMIDINECARBOXAMIDE
METABOLITE -> PARENT
(DEALKYLATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; URINE
Structure of 3-((5-(2-AMINOPYRIMIDINE-5-CARBOXAMIDO)-7-METHOXY-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-8-YL)OXY)PROPANOIC ACID
METABOLITE -> PARENT
(DEALKYLATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; URINE
Structure of 2-AMINO-N-(8-(3-HYDROXYPROPOXY)-7-METHOXY-2,3-DIHYDROIMIDAZO(1,2-C)QUINAZOLIN-5-YL)PYRIMIDINE-5-CARBOXAMIDE
METABOLITE -> PARENT
(DEALKYLATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; URINE
Structure of BAY-84-5975
METABOLITE ACTIVE -> PARENT
(OXIDATION BY CYP3A4), The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; PLASMA; URINE
Related Record Type Details
Structure of COPANLISIB
ACTIVE MOIETY
The six healthy male volunteers received a single i.v. infusion of 12 mg copanlisib (2.76 MBq (14C)copanlisib) in a total volume of 40 mL as a 1-h infusion in the morning, 1-h after a light breakfast. 5 Caucasians and 1 Asian with an age 54.8 +/- 5.2 yeas (mean +/- SD, range: 47-61 years) and a BMI of 24.8 kg/m^2. Non-smokers and reported at the most light alcohol use.
AMOUNT EXCRETED
FECAL; PLASMA; URINE
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
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DISCLAIMER
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