Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H17ClN6O |
Molecular Weight | 416.863 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](NC1=C2N=CNC2=NC=N1)C3=CC4=C(C(Cl)=CC=C4)C(=O)N3C5=CC=CC=C5
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
Molecular Formula | C22H17ClN6O |
Molecular Weight | 416.863 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://adisinsight.springer.com/drugs/800035173Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24211136
Sources: http://adisinsight.springer.com/drugs/800035173
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
Sources: http://adisinsight.springer.com/drugs/800035173
Curator's Comment: # Intellikine (owned by Takeda)
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24211136 |
2.5 nM [IC50] | ||
Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24211136 |
27.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | COPIKTRA Approved UseCOPIKTRA 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 Date2018 |
|||
Primary | COPIKTRA Approved UseCOPIKTRA 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 Date2018 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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) Sources: Aspartate aminotransferase increased (grade 3, 1 patient) Rash (grade 3, 1 patient) |
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%) Sources: Page: p. 137Sepsis (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%) |
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%) Sources: Colitis (36%) Infection (36%) Rash (36%) Diarrhea (29%) Colitis (29%) Rash (29%) |
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%) Sources: 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%) |
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 Health Status: unhealthy Sources: |
Other AEs: Infection, Diarrhea... Other AEs: Infection (grade 5|serious, 31%) Sources: Diarrhea (grade 5|serious, 18%) Colitis (grade 5|serious, 18%) Epidermal and dermal conditions (grade 5|serious, 5%) Pneumonitis (grade 5|serious, 5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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 ( Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211155Orig1Orig2s000MultidisciplineR.pdf#page=64 Page: 64.0 |
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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 ( Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211155Orig1Orig2s000MultidisciplineR.pdf#page=64 Page: 64.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211155Orig1Orig2s000MultidisciplineR.pdf#page=39 Page: 39.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. | 2013 Nov 21 |
|
Novel phosphoinositide 3-kinase δ,γ inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis. | 2014 Feb |
Sample Use Guides
In Vivo Use Guide
Sources: http://adisinsight.springer.com/drugs/800035173
25-75 mg twice daily for five to 28 days
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25258342
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
Edited
Sat Dec 16 01:41:55 GMT 2023
by
admin
on
Sat Dec 16 01:41:55 GMT 2023
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Record UNII |
610V23S0JI
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Record Status |
Validated (UNII)
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Record Version |
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Official Name | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Code | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2152
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FDA ORPHAN DRUG |
703019
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FDA ORPHAN DRUG |
399913
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NCI_THESAURUS |
C129825
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FDA ORPHAN DRUG |
394413
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EU-Orphan Drug |
EU/3/13/1125
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Code System | Code | Type | Description | ||
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DB11952
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50905713
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CHEMBL3039502
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C99225
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2058509
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m12094
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AB-61
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5296
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9856
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610V23S0JI
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Duvelisib
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Duvelisib
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DTXSID80152697
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1201438-56-3
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PRIMARY | |||
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100000166112
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PRIMARY | |||
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610V23S0JI
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SUB180102
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
IC50
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EXCRETED UNCHANGED |
FECAL
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR |
Kd
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METABOLIC ENZYME -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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SOLVATE->ANHYDROUS | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
Kd
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CUMULATIVE EXCRETION |
FECAL
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METABOLIC ENZYME -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ROUTE OF ADMINISTRATION PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | PHARMACOKINETIC |
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ROUTE OF ADMINISTRATION PHARMACOKINETIC |