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Details

Stereochemistry ACHIRAL
Molecular Formula C23H28N8O4.2ClH.4H2O
Molecular Weight 625.5034
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of COPANLISIB HYDROCHLORIDE HYDRATE

SMILES

COc1c(ccc2c1N=C(N=C(c3c[nH]c(=N)nc3)O)N4CCN=C24)OCCCN5CCOCC5.Cl.Cl.O.O.O.O

InChI

InChIKey=PRZNRMHJLYLVBJ-UHFFFAOYSA-N
InChI=1S/C23H28N8O4.2ClH.4H2O/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;4*1H2

HIDE SMILES / InChI

Molecular Formula C23H28N8O4
Molecular Weight 480.5205
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.50526086E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
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
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
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
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
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:
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)
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:
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%)
Neutropenia (5%)
Hypertension (5%)
Pneumonitis (2%)
Hyperglycemia (2%)
Sources:
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%)
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: 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:
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

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical 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

Drug as victim

TargetModalityActivityMetaboliteClinical 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
Page: 65.0
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
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

Sample Use Guides

60 mg in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle
Route of Administration: Oral
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 Sat Jun 26 05:31:43 UTC 2021
Edited
by admin
on Sat Jun 26 05:31:43 UTC 2021
Record UNII
W421JK3CPA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
COPANLISIB HYDROCHLORIDE HYDRATE
Common Name English
COPANLISIB HYDROCHLORIDE TETRAHYDRATE
Common Name English
ALIQOPA
Brand Name English
COPANLISIB HYDROCHLORIDE HYDRATE [JAN]
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)-, HYDROCHLORIDE, HYDRATE (1:2:4)
Systematic Name English
COPANLISIB DIHYDROCHLORIDE TETRAHYDRATE
Common Name English
Code System Code Type Description
CAS
1402152-46-8
Created by admin on Sat Jun 26 05:31:43 UTC 2021 , Edited by admin on Sat Jun 26 05:31:43 UTC 2021
PRIMARY
FDA UNII
W421JK3CPA
Created by admin on Sat Jun 26 05:31:43 UTC 2021 , Edited by admin on Sat Jun 26 05:31:43 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY