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

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H18FN7O
Molecular Weight 415.423
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IDELALISIB

SMILES

CC[C@H](NC1=C2N=CNC2=NC=N1)C3=NC4=C(C(=O)N3C5=CC=CC=C5)C(F)=CC=C4

InChI

InChIKey=IFSDAJWBUCMOAH-HNNXBMFYSA-N
InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including http://link.springer.com/article/10.1007/s40265-014-0285-6

Idelalisib is a first-in-class selective inhibitor of adenosine-5'-triphosphate (ATP) binding to PI3Kdelta kinase, resulting in inhibition of the P13K signalling pathway in malignant B cells. The compound is approved for the treatment of several types of blood cancer. Idelalisib is intended to be used in combination with rituximab as second or subsequent line therapy for the treatment of chronic lymphocytic leukaemia. The drug may cause fatal and/or severe diarrhea or colitis, hepatotoxicity, pneumonitis and intestinal perforation.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Ibrutinib can cross the blood-brain barrier (1–7% of the dose found in cerebral spinal fluid).

Originator

Approval Year

2014
494
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 2.5 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
ZYDELIG

Approved Use

Indicated for the treatment of patients with: 1) relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; 3) relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.

Launch Date

2014
Primary
Approved
8429
ZYDELIG

Approved Use

Indicated for the treatment of patients with: 1) relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; 3) relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.

Launch Date

2014
Primary
Approved
8429
ZYDELIG

Approved Use

Indicated for the treatment of patients with: 1) relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; 3) relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.

Launch Date

2014
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.953 ng/mL
OTHER GOV
https://www.ema.europa.eu/en/documents/product-information/zydelig-epar-product-information_en.pdf
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IDELALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2647.5 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01282424
150 mg single, oral
dose: 150 mg
route of administration: oral
experiment type: single
co-administered:
IDELALISIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
2258.8 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01282424
150 mg 2 times / day multiple, oral
dose: 150 mg
route of administration: oral
experiment type: multiple
co-administered:
IDELALISIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10.439 ng × h/mL
OTHER GOV
https://www.ema.europa.eu/en/documents/product-information/zydelig-epar-product-information_en.pdf
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IDELALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9094.76 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01282424
150 mg single, oral
dose: 150 mg
route of administration: oral
experiment type: single
co-administered:
IDELALISIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
9293.39 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01282424
150 mg 2 times / day multiple, oral
dose: 150 mg
route of administration: oral
experiment type: multiple
co-administered:
IDELALISIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.2 h
OTHER GOV
https://www.ema.europa.eu/en/documents/product-information/zydelig-epar-product-information_en.pdf
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IDELALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Other AEs: Diarrhea, Pneumonia...
Other AEs:
Diarrhea (grade 3, 25%)
Pneumonia (grade 3, 25%)
Edema peripheral (grade 3, 25%)
AST increased (grade 3, 50%)
ALT increased (grade 3, 50%)
Absolute neutrophil count decreased (grade 3, 50%)
Platelets decreased (grade 3, 50%)
Vomiting (all grades, 25%)
Rash (all grades, 25%)
Chills (all grades, 25%)
Fatigue (all grades, 25%)
Constipation (all grades, 25%)
Nausea (all grades, 25%)
Insomnia (all grades, 25%)
Edema peripheral (all grades, 25%)
Arterial pressure NOS increased (all grades, 25%)
Bilirubin increased (all grades, 25%)
Glucose increased (all grades, 25%)
Glucose decreased (all grades, 25%)
Hemoglobin decreased (all grades, 25%)
Pyrexia (all grades, 25%)
Night sweats (all grades, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Disc. AE: Hepatotoxicity, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity (10%)
Diarrhea (10%)
Colitis (10%)
Transaminases increased (15%)
Diarrhea (15%)
Colitis (15%)
Rash (15%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Other AEs: Hepatotoxicity, Diarrhea...
Other AEs:
Hepatotoxicity (serious|grade 5, 14%)
Diarrhea (serious|grade 5, 14%)
Colitis (serious|grade 5, 14%)
Pneumonitis (serious|grade 5)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Arterial pressure NOS increased all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Bilirubin increased all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Chills all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Constipation all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Edema peripheral all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Fatigue all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Glucose decreased all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Glucose increased all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Hemoglobin decreased all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Insomnia all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Nausea all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Night sweats all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Pyrexia all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Rash all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Vomiting all grades, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Diarrhea grade 3, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Edema peripheral grade 3, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Pneumonia grade 3, 25%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
ALT increased grade 3, 50%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
AST increased grade 3, 50%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Absolute neutrophil count decreased grade 3, 50%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Platelets decreased grade 3, 50%
350 mg 2 times / day multiple, oral
Highest studied dose
Dose: 350 mg, 2 times / day
Route: oral
Route: multiple
Dose: 350 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
unhealthy, 64 years (range: 32-91 years)
n = 4
Health Status: unhealthy
Condition: non-Hodgkin lymphoma
Age Group: 64 years (range: 32-91 years)
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/24615776
Colitis 10%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Diarrhea 10%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Hepatotoxicity 10%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Colitis 15%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Diarrhea 15%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Rash 15%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Transaminases increased 15%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, 71 years (range: 47 - 92 years)
n = 110
Health Status: unhealthy
Condition: Relapsed Chronic Lymphocytic Leukemia
Age Group: 71 years (range: 47 - 92 years)
Sex: M+F
Population Size: 110
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Pneumonitis serious|grade 5
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Colitis serious|grade 5, 14%
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Diarrhea serious|grade 5, 14%
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Hepatotoxicity serious|grade 5, 14%
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inducer
781
inhibitor
1767

inducer
389
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP3A
214

CYP2C19
1478

P-gp
1461

OATP1B1
788

OATP1B3
706

UGT1A1
204

CYP2C8
911

CYP1A
72

CYP2B6
810

CYP1A2
1524

BCRP
699

OAT1
599

OAT3
642

OCT2
647
aldehyde oxidase
16

UGT1A4
347

P-gp
1537

BCRP
561

OATP1B1
406

OATP1B3
350

OCT2
355

OAT1
326

OAT3
339
CYP1A2
701

CYP2B6
547

CYP2C8
168

CYP2C19
293

P-gp
257

UGT1A1
69

UGT1A4
8

aldehyde oxidase
1
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OAT1
603
 no [IC50 >10 uM]
OAT3
644
 no [IC50 >10 uM]
OCT2
648
 no [IC50 >10 uM]
BCRP
773
 no [IC50 >100 uM]
BCRP
773
 no [IC50 >100 uM]
GS-563117
1
CYP1A
121
 no [IC50 >100 uM]
CYP1A2
1692
 no [IC50 >100 uM]
GS-563117
1
CYP2B6
1001
 no [IC50 >100 uM]
GS-563117
1
CYP2C9
1819
 no [IC50 >100 uM]
CYP2D6
1891
 no [IC50 >100 uM]
GS-563117
1
OAT1
603
 no [IC50 >100 uM]
GS-563117
1
OAT3
644
 no [IC50 >100 uM]
GS-563117
1
P-gp
1650
 no [IC50 >100 uM]
GS-563117
1
CYP2B6
1001
 no [IC50 >25 uM]
CYP1A2
1692
 no
CYP2B6
1001
 no
CYP3A4
1925
 no
OATP1B1
803
 yes [IC50 10 uM]
no (co-administration study)
Comment: No changes in exposure to rosuvastatin (OAT1B1 and OATP1B3) or digoxin (P-gp) were observed.
Page: 7.0
UGT1A1
254
 yes [IC50 22 uM]
GS-563117
1
OATP1B1
803
 yes [IC50 26 uM]
GS-563117
1
OATP1B3
715
 yes [IC50 36 uM]
GS-563117
1
CYP2C8
965
 yes [IC50 39.8 uM]
GS-563117
1
UGT1A1
254
 yes [IC50 42 uM]
CYP3A
298
 yes [IC50 44 uM]
yes (co-administration study)
Comment: Idelalisib increased midazolam AUC by 5.4-fold; therefore, idelalisib should not be coadministered with sensitive CYP3A substrates.
Page: 7.0
CYP3A
298
 yes [IC50 5.1 uM]
GS-563117
1
OCT2
648
 yes [IC50 50 uM]
GS-563117
1
CYP2C19
1553
 yes [IC50 60.4 uM]
GS-563117
1
OATP1B3
715
 yes [IC50 7 uM]
no (co-administration study)
Comment: No changes in exposure to rosuvastatin (OAT1B1 and OATP1B3) or digoxin (P-gp) were observed.
Page: 7.0
CYP2C19
1553
 yes [IC50 76 uM]
yes (co-administration study)
Comment: Relatively few patients were coadministered CYP2C8, CYP2C9 or UGT1A1 substrates, but about 30% of patients enrolled in NHL and CLL trials were coadministered sensitive CYP2C19 substrates, including lansoprazole and omeprazole. The incidence of diarrhea and rash were higher in patients taking PPI (Section 2.1.1). These adverse events are associated with both PPI (1% to 4%) [PMC2014999] and idelalisib. The exposure to idelalisib is similar in patients taking ARA as compared to patients not taking these agents. Overlapping adverse events or an increased exposure to PPI (CYP2C19 substrates) could explain the increased incidence of adverse events.
Page: 7.0
P-gp
1650
 yes [IC50 8 uM]
no (co-administration study)
Comment: No changes in exposure to rosuvastatin (OAT1B1 and OATP1B3) or digoxin (P-gp) were observed.
Page: 7.0
CYP2C9
1819
 yes [IC50 90.7 uM]
GS-563117
1
CYP2C19
1553
 yes
CYP2C8
965
 yes
CYP2C8
965
 yes
CYP2C9
1819
 yes
P-gp
1650
 yes
UGT1A1
254
 yes
UGT1A4
80
 yes
aldehyde oxidase
8
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
OAT1
326
 no
OAT3
339
 no
OATP1B1
406
 no
OATP1B1
406
 no
GS-563117
1
OATP1B3
350
 no
OATP1B3
350
 no
GS-563117
1
OCT2
355
 no
BCRP
561
 yes
BCRP
561
 yes
GS-563117
1
P-gp
1537
 yes
P-gp
1537
 yes
GS-563117
1
UGT1A4
347
 yes
aldehyde oxidase
16
 yes
CYP3A4
1737
 yes
yes (co-administration study)
Comment: Rifampin decreased idelalisib AUC by 75%
Page: 7.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:82701
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82701
ChemicalBook
CB32538915
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32538915
ChemicalBook
CB62638450
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62638450
MolPort
MolPort-016-633-355
https://www.molport.com/shop/molecule-link/MolPort-016-633-355
MolPort
MolPort-042-652-833
https://www.molport.com/shop/molecule-link/MolPort-042-652-833
Selleck Chemicals
CAL-101
http://www.selleckchem.com/products/CAL-101.html
ZINC
ZINC000013986658
http://zinc15.docking.org/substances/ZINC000013986658
eMolecules
36516858
https://www.emolecules.com/cgi-bin/more?vid=36516858
PubMed

PubMed

TitleDatePubMed
CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability.
2011 Jan 13
The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells.
2013
Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.
2013 Jan
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.
2013 Jun 15
Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.
2014 Mar 13
Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.
2014 May 29
Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma.
2014 May 29
Clinical drug interaction profile of idelalisib in healthy subjects.
2015 Aug
Patents

Patents

07932260
1
08207153
1
08779131
1
20080275067
2

Sample Use Guides

In Vivo Use Guide
The recommended dose is 150 mg taken orally, twice daily
Route of Administration: Oral
In Vitro Use Guide
Treatment of primary CLL cells (n =14) co-cultured with HS5 stromal cells with 100 nM idelalisib results in decreased AKT phosphorylation and inhibition of BCR mediated signaling pathways.
Name Type Language
IDELALISIB
DASH   INN   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
CAL-101
Code English
GS-1101
Code English
4(3H)-QUINAZOLINONE, 5-FLUORO-3-PHENYL-2-((1S)-1-(1H-PURIN-6-YLAMINO)PROPYL)-
Systematic Name English
ZYDELIG
Brand Name English
IDELALISIB [JAN]
Common Name English
idelalisib [INN]
Common Name English
IDELALISIB [ORANGE BOOK]
Common Name English
5-FLUORO-3-PHENYL-2-((S)-1-(9H-PURIN-6-YLAMINO)-PROPYL)-3H-QUINAZOLIN-4-ONE
Systematic Name English
IDELALISIB [VANDF]
Common Name English
IDELALISIB [MI]
Common Name English
4(3H)-QUINAZOLINONE, 5-FLUORO-3-PHENYL-2-((1S)-1-(9H-PURIN-6-YLAMINO)PROPYL)-
Systematic Name English
Idelalisib [WHO-DD]
Common Name English
IDELALISIB [USAN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 405913
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
EMA ASSESSMENT REPORTS ZYDELIG (AUTHORIZED: LYMPHOMA, NON-HODGKIN)
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 405813
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
WHO-ATC L01XX47
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
NDF-RT N0000175605
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 405613
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 412613
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
EMA ASSESSMENT REPORTS ZYDELIG (AUTHORIZED: LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL)
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 405713
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
EU-Orphan Drug EU/3/13/1160
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 347511
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
NCI_THESAURUS C2152
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
FDA ORPHAN DRUG 412513
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
Code System Code Type Description
DRUG BANK
DB09054
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
NDF-RT
N0000175082
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY Kinase Inhibitors [MoA]
SMS_ID
100000151771
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
RXCUI
1544460
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY RxNorm
LACTMED
Idelalisib
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
MERCK INDEX
m11752
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
EVMPD
SUB126168
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
CAS
870281-82-6
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
CHEBI
82701
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
EPA CompTox
DTXSID701007266
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
NCI_THESAURUS
C78825
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
WIKIPEDIA
Idelalisib
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
IUPHAR
6741
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
DAILYMED
YG57I8T5M0
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
FDA UNII
YG57I8T5M0
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
DRUG CENTRAL
4878
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
INN
9624
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
ChEMBL
CHEMBL2216870
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
USAN
AB-74
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
PUBCHEM
11625818
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
NCI_THESAURUS
C78825
Created by admin on Sat Dec 16 01:29:15 GMT 2023 , Edited by admin on Sat Dec 16 01:29:15 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of IDELALISIB
METABOLITE (PARENT)
Structure of GS-563129
METABOLITE (PARENT)
Structure of Allantoin
METABOLITE (PARENT)
Structure of URIC ACID
METABOLITE INACTIVE (PARENT)
Structure of GS-563117
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966