Details
Stereochemistry | ACHIRAL |
Molecular Formula | C23H28N8O4.2ClH |
Molecular Weight | 553.442 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.COC1=C(OCCCN2CCOCC2)C=CC3=C1N=C(NC(=O)C4=CN=C(N)N=C4)N5CCN=C35
InChI
InChIKey=STGQPVQAAFJJFX-UHFFFAOYSA-N
InChI=1S/C23H28N8O4.2ClH/c1-33-19-17(35-10-2-6-30-8-11-34-12-9-30)4-3-16-18(19)28-23(31-7-5-25-20(16)31)29-21(32)15-13-26-22(24)27-14-15;;/h3-4,13-14H,2,5-12H2,1H3,(H2,24,26,27)(H,28,29,32);2*1H
DescriptionSources: http://adisinsight.springer.com/drugs/800031792Curator'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
Sources: http://adisinsight.springer.com/drugs/800031792
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24170767 |
3.7 nM [IC50] | ||
Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24170767 |
0.7 nM [IC50] | ||
Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24170767 |
0.5 nM [IC50] | ||
Target ID: CHEMBL3267 |
6.4 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ALIQOPA Approved UseALIQOPA 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 Date2017 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
463 ng/mL |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1570 ng × h/mL |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
39.1 h |
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
Dose | Population | Adverse 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: |
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: |
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased... Dose limiting toxicities: Alanine aminotransferase increased (grade 3, 1 patient) Sources: 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) |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
Disc. AE: Hyperglycemia, Neutropenia... AEs leading to discontinuation/dose reduction: Hyperglycemia (7%) Sources: Neutropenia (5%) Hypertension (5%) Pneumonitis (2%) Hyperglycemia (2%) |
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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: Page: зю 99 |
Disc. AE: Thrombocytopenia, Neutropenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (3%) Sources: Page: зю 99Neutropenia (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%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
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: |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: |
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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: 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: Page: зю 99 |
unhealthy, adult n = 168 Health Status: unhealthy Condition: hematologic malignancies Age Group: adult Sex: M+F Population Size: 168 Sources: Page: зю 99 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [IC50 0.09 uM] | ||||
yes [IC50 10.8 uM] | ||||
yes [IC50 11.5 uM] | ||||
yes [IC50 7 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf#page=65 Page: 65.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02369016
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24170767
Several breast cancer, endometrial cancer, and hematologic tumor cell lines were particularly sensitive to Copanlisib, with IC50 values less than 10nmol/L
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C2152
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03ZI7RZ52O
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173081
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C138994
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66562429
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DTXSID301027642
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100000170810
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CD-72
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DBSALT002581
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CHEMBL3218576
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1402152-13-9
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SUB184953
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m12036
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ACTIVE MOIETY
SUBSTANCE RECORD