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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H17ClN6O
Molecular Weight 416.8637
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DUVELISIB

SMILES

C[C@@]([H])(c1cc2cccc(c2c(=O)n1-c3ccccc3)Cl)Nc4c5c([nH]cn5)ncn4

InChI

InChIKey=SJVQHLPISAIATJ-ZDUSSCGKSA-N
InChI=1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H17ClN6O
Molecular Weight 416.8637
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24211136

Duvelisib (IPI-145), is an orally available, small-molecule, selective dual inhibitor of phosphatidylinositol 3 kinase (PI3K) δ and γ isoforms originated by Intellikine (owned by Takeda) and developed by Infinity Pharmaceuticals. Orally administered duvelisib was rapidly absorbed, with a dose-proportional increase in exposure. The compound produced a half-life of approximately 7-12 hours, following 14 days of dosing. Duvelisib exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. Duvelisib blockade of PI3K-δ and PI3K-γ potentially lead to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases. The molecule is in phase III development as a combination therapy for patients with haematological malignancies such as chronic lymphocytic leukemia and follicular lymphoma.

Originator

Curator's Comment:: # Intellikine (owned by Takeda)

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.5 nM [IC50]
27.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COPIKTRA

Approved Use

COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with: • Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies. • Relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies.

Launch Date

1.53766081E12
Primary
COPIKTRA

Approved Use

COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with: • Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies. • Relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies.

Launch Date

1.53766081E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1062 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DUVELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.5 μg/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DUVELISIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7098.4 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DUVELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.9 μg × h/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DUVELISIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.8 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DUVELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.7 h
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DUVELISIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day steady, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 2
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 2
Sources:
DLT: Alanine aminotransferase increase, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increase (grade 3, 1 patient)
Aspartate aminotransferase increased (grade 3, 1 patient)
Rash (grade 3, 1 patient)
Sources:
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 6
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 6
Sources:
DLT: Cellulitis...
Dose limiting toxicities:
Cellulitis (grade 3, 1 patient)
Sources:
15 mg 2 times / day steady, oral
Dose: 15 mg, 2 times / day
Route: oral
Route: steady
Dose: 15 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 7
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 7
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 1 patient)
Sources:
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Disc. AE: Transaminases increased, Sepsis...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (1%)
Sepsis (1%)
Transaminases increased (4%)
Neutropenia (3%)
Febrile neutropenia (2%)
Lipase increased (1%)
Diarrhea (19%)
Colitis (19%)
Rash (8%)
Pneumonia (10%)
Neutropenia (8%)
Transaminases increased (6%)
Pyrexia (4%)
Anemia (3%)
Febrile neutropenia (3%)
Lipase increased (3%)
Thrombocytopenia (3%)
Sources: Page: p. 137
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Disc. AE: Diarrhea, Colitis...
AEs leading to
discontinuation/dose reduction:
Diarrhea (36%)
Colitis (36%)
Infection (36%)
Rash (36%)
Diarrhea (29%)
Colitis (29%)
Rash (29%)
Sources:
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Other AEs: ALT increased, AST increased...
Other AEs:
ALT increased (grade 3-4, 40%)
AST increased (grade 3-4, 13.3%)
Neutropenia (grade 3-4, 33.3%)
Anemia (grade 3, 13.3%)
Diarrhea (grade 3, 33.3%)
Pyrexia (grade 3, 6.7%)
Nausea (grade 3, 6.7%)
Rash maculo-papular (grade 3, 13.3%)
Thrombocytopenia (grade 1-2, 13.3%)
Fatigue (grade 1-2, 46.7%)
Cough (grade 1-2, 46.7%)
Headache (grade 1-2, 26.7%)
Decreased appetite (grade 1-2, 26.7%)
Dyspnoea (grade 1-2, 40%)
Rash (grade 1-2, 26.7%)
Upper respiratory tract infection (grade 1-2, 13.3%)
Vomiting (grade 1-2, 6.7%)
Chills (grade 1-2, 13.3%)
Myalgia (grade 1-2, 26.7%)
Edema peripheral (grade 1-2, 26.7%)
Oropharyngeal pain (grade 1-2, 20%)
Stomatitis (grade 1-2, 26.7%)
Sources:
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
Other AEs: Infection, Diarrhea...
Other AEs:
Infection (grade 5|serious, 31%)
Diarrhea (grade 5|serious, 18%)
Colitis (grade 5|serious, 18%)
Epidermal and dermal conditions (grade 5|serious, 5%)
Pneumonitis (grade 5|serious, 5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Alanine aminotransferase increase grade 3, 1 patient
DLT
100 mg 2 times / day steady, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 2
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 2
Sources:
Aspartate aminotransferase increased grade 3, 1 patient
DLT
100 mg 2 times / day steady, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 2
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 2
Sources:
Rash grade 3, 1 patient
DLT
100 mg 2 times / day steady, oral
Highest studied dose
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 2
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 2
Sources:
Cellulitis grade 3, 1 patient
DLT
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 6
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 6
Sources:
Neutropenia grade 4, 1 patient
DLT
15 mg 2 times / day steady, oral
Dose: 15 mg, 2 times / day
Route: oral
Route: steady
Dose: 15 mg, 2 times / day
Sources:
unhealthy, 66.5 years (range: 25-86 years)
n = 7
Health Status: unhealthy
Age Group: 66.5 years (range: 25-86 years)
Sex: M+F
Population Size: 7
Sources:
Lipase increased 1%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Sepsis 1%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Transaminases increased 1%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Pneumonia 10%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Colitis 19%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Diarrhea 19%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Febrile neutropenia 2%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Anemia 3%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Febrile neutropenia 3%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Lipase increased 3%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Neutropenia 3%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Thrombocytopenia 3%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Pyrexia 4%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Transaminases increased 4%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Transaminases increased 6%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Neutropenia 8%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Rash 8%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources: Page: p. 137
unhealthy, 67 years (range: 30 - 90 years)
n = 442
Health Status: unhealthy
Condition: Hematologic Malignancies
Age Group: 67 years (range: 30 - 90 years)
Sex: M+F
Population Size: 442
Sources: Page: p. 137
Colitis 29%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Diarrhea 29%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Rash 29%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Colitis 36%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Diarrhea 36%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Infection 36%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Rash 36%
Disc. AE
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, 69 years (range: 39 - 90 years
n = 158
Health Status: unhealthy
Condition: CLL or SLL
Age Group: 69 years (range: 39 - 90 years
Sex: M+F
Population Size: 158
Sources:
Chills grade 1-2, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Thrombocytopenia grade 1-2, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Upper respiratory tract infection grade 1-2, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Oropharyngeal pain grade 1-2, 20%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Decreased appetite grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Edema peripheral grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Headache grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Myalgia grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Rash grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Stomatitis grade 1-2, 26.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Dyspnoea grade 1-2, 40%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Cough grade 1-2, 46.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Fatigue grade 1-2, 46.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Vomiting grade 1-2, 6.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Anemia grade 3, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Rash maculo-papular grade 3, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Diarrhea grade 3, 33.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Nausea grade 3, 6.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Pyrexia grade 3, 6.7%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
AST increased grade 3-4, 13.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Neutropenia grade 3-4, 33.3%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
ALT increased grade 3-4, 40%
75 mg 2 times / day steady, oral
MTD
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 70 years (range: 42-78)
n = 15
Health Status: unhealthy
Age Group: 70 years (range: 42-78)
Sex: M+F
Population Size: 15
Sources:
Colitis grade 5|serious, 18%
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
Diarrhea grade 5|serious, 18%
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
Infection grade 5|serious, 31%
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
Epidermal and dermal conditions grade 5|serious, 5%
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
Pneumonitis grade 5|serious, 5%
25 mg 2 times / day steady, oral
Recommended
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: In a dedicated drug-interaction trial in healthy subjects, midazolam (a CYP3A4 substrate) single dose Cmax and AUC were increased by 120% and 330% respectively, when co-administered with duvelisib (
Page: 64.0
yes
yes (co-administration study)
Comment: In a dedicated drug-interaction trial in healthy subjects, midazolam (a CYP3A4 substrate) single dose Cmax and AUC were increased by 120% and 330% respectively, when co-administered with duvelisib (
Page: 64.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes
yes
yes
yes (co-administration study)
Comment: In a dedicated drug-interaction trial in healthy subjects (N=16), concomitant ketoconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) increased duvelisib Cmax and AUC by 66% and 295% respectively
Page: 39.0
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models.
2013 Nov 21
IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells.
2014 Dec 4
PI3-kinase inhibitors in chronic lymphocytic leukemia.
2014 Mar
The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL.
2015 Sep
Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection.
2016 Jun 28
Patents

Sample Use Guides

25-75 mg twice daily for five to 28 days
Route of Administration: Oral
0.25 to 5 uM IPI-145 exhibited concentration- and time-dependent induction of cytotoxicity in primary chronic lymphocytic leukemia cells
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:22:26 UTC 2021
Edited
by admin
on Sat Jun 26 03:22:26 UTC 2021
Record UNII
610V23S0JI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DUVELISIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
1(2H)-ISOQUINOLINONE, 8-CHLORO-2-PHENYL-3-((1S)-1-(9H-PURIN-6-YLAMINO)ETHYL)-
Systematic Name English
IPI-145
Code English
DUVELISIB [INN]
Common Name English
(S)-3-(1-(9H-PURIN-6-YLAMINO)ETHYL)-8-CHLORO-2-PHENYLISOQUINOLIN-1(2H)-ONE
Systematic Name English
DUVELISIB [MI]
Common Name English
INK-1197
Code English
DUVELISIB [WHO-DD]
Common Name English
DUVELISIB [ORANGE BOOK]
Common Name English
DUVELISIB [USAN]
Common Name English
INK-1147
Code English
Classification Tree Code System Code
NCI_THESAURUS C2152
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
FDA ORPHAN DRUG 703019
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
FDA ORPHAN DRUG 394413
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
FDA ORPHAN DRUG 399913
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
EU-Orphan Drug EU/3/13/1125
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
Code System Code Type Description
DRUG BANK
DB11952
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
PUBCHEM
50905713
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
ChEMBL
CHEMBL3039502
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
NCI_THESAURUS
C99225
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
RXCUI
2058509
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
MERCK INDEX
M12094
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
DRUG CENTRAL
5296
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
INN
9856
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
LACTMED
Duvelisib
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
EPA CompTox
1201438-56-3
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
CAS
1201438-56-3
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
FDA UNII
610V23S0JI
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
EVMPD
SUB180102
Created by admin on Sat Jun 26 03:22:26 UTC 2021 , Edited by admin on Sat Jun 26 03:22:26 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
EXCRETED UNCHANGED
FECAL
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
Kd
METABOLIC ENZYME -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
Kd
CUMULATIVE EXCRETION
FECAL
METABOLIC ENZYME -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
MAXIMUM TOLERATED DOSE PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC