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

Details

Stereochemistry ACHIRAL
Molecular Formula C28H22F3N7O.ClH.2H2O
Molecular Weight 602.0083
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NILOTINIB HYDROCHLORIDE DIHYDRATE

SMILES

Cc1ccc(cc1Nc2nccc(-c3cccnc3)n2)C(=Nc4cc(cc(c4)-n5cc(C)nc5)C(F)(F)F)O.Cl.O.O

InChI

InChIKey=SDOLNFCUZATHSO-UHFFFAOYSA-N
InChI=1S/C28H22F3N7O.ClH.2H2O/c1-17-5-6-19(10-25(17)37-27-33-9-7-24(36-27)20-4-3-8-32-14-20)26(39)35-22-11-21(28(29,30)31)12-23(13-22)38-15-18(2)34-16-38;;;/h3-16H,1-2H3,(H,35,39)(H,33,36,37);1H;2*1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Molecular Formula C28H22F3N7O
Molecular Weight 529.5168
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16721371 | https://www.ncbi.nlm.nih.gov/pubmed/19920925

Nilotinib (AMN107, trade name Tasigna) is a kinase inhibitor indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included imatinib. Nilotinib is an inhibitor of the Bcr-Abl kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of Abl protein. In vitro, nilotinib inhibited Bcr-Abl mediated proliferation of murine leukemic cell lines and human cell lines derived from Ph+ CML patients. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from Bcr-Abl kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine Bcr-Abl xenograft model. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: Bcr-Abl (20-60 nM), PDGFR (69 nM) and c-Kit (210 nM). Nilotinib is currently being trialed in people with Parkinson's disease, as it appears to be able to halt progression of the disease and even improve their symptoms. The drug also has a number of adverse effects typical of anti-cancer drugs: a headache, fatigue, gastrointestinal problems such as nausea, vomiting, diarrhea and constipation, muscle and joint pain, rash and other skin conditions, flu-like symptoms, and reduced blood cell count. Less typical side effects are those of the cardiovascular system, such as hypertension (high blood pressure), various types of arrhythmia, and prolonged QT interval. Interaction of nilotinib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions. Nilotinib is an inhibitor of OATP-1B1 transporter but not for OATP-1B3. Main metabolic pathways identified in healthy subjects are oxidation and hydroxylation. Nilotinib is the main circulating component in the serum. None of the metabolites contributes significantly to the pharmacological activity of nilotinib.

Originator

Curator's Comment:: # Novartis Pharmaceuticals Corporation

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.33 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TASIGNA

Approved Use

Tasigna is a kinase inhibitor indicated for: The treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The treatment of chronic phase (CP) and accelerated phase (AP) Ph+ CML in adult patients resistant to or intolerant to prior therapy that included imatinib. (1.2) 1.1 Newly Diagnosed Ph+ CML-CP Tasigna (nilotinib) is indicated for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The effectiveness of Tasigna is based on major molecular response and cytogenetic response rates [see Clinical Studies (14.1)

Launch Date

1.19361595E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1550 ng/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2300 ng/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
3320 ng/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6010 ng/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
2190 ng/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2490 ng/mL
1200 mg 1 times / day steady-state, oral
dose: 1200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
403 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
402.715 ng/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
405.111 ng/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
1360 ng/mL
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: FASTED
1595 ng/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
12700 ng × h/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
18200 ng × h/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
24500 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
43100 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
26600 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
28000 ng × h/mL
1200 mg 1 times / day steady-state, oral
dose: 1200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4480 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
14383.076 ng*h/mL
230 mg/m^2 2 times / day steady, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: steady
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
15129.182 ng*h/mL
230 mg/m^2 2 times / day steady, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: steady
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
2795.78199999999 ng*h/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
3393.296 ng*h/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
4160.969 ng*h/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
5707.368 ng*h/mL
230 mg/m^2 single, oral
dose: 230 mg/m^2
route of administration: oral
experiment type: single
co-administered:
NILOTINIB plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status:
11865 ng × h/mL
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: FASTED
13656 ng × h/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NILOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.6%
NILOTINIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Disc. AE: Thrombocytopenia, Neutropenia...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (5 patients)
Neutropenia (1 patient)
Bilirubin increased (2 patients)
Hepatotoxicity (2 patients)
Skin rash (1 patient)
Sources:
600 mg 2 times / day steady, oral
MTD
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 56.2 ± 15.3 years
n = 18
Health Status: unhealthy
Condition: CML: blastic phase, accelerated phase, and chronic phase) | Ph-positive ALL
Age Group: 56.2 ± 15.3 years
Sex: M+F
Population Size: 18
Sources:
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Disc. AE: Rash, Pancreatitis...
AEs leading to
discontinuation/dose reduction:
Rash (1 patient)
Pancreatitis (1 patient)
Myocardial infarction (1 patient)
Thrombocytopenia (grade 3, 1 patient)
Neutropenia (grade 3, 1 patient)
Sources:
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Other AEs: Rash, Fatigue...
Other AEs:
Rash (grade 3-4, 3%)
Fatigue (grade 3-4, 3%)
Bilirubin total increased (grade 3-4, 3%)
Conjugated bilirubin level increased (grade 3-4, 3%)
Bilirubin unconjugated increased (grade 3-4, 6%)
Lipase increased (grade 3-4, 3%)
ALT increased (grade 3-4, 9%)
Aspartate aminotransferase increased (grade 3-4, 9%)
Thrombocytopenia (grade 3-4, 17%)
Neutropenia (grade 3-4, 14%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Neutropenia 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Skin rash 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Bilirubin increased 2 patients
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Hepatotoxicity 2 patients
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Thrombocytopenia 5 patients
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 56 years (range: 26-85 years)
n = 132
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - chronic phase ((CML-CP)
Age Group: 56 years (range: 26-85 years)
Sex: M+F
Population Size: 132
Sources:
Myocardial infarction 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Pancreatitis 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Rash 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Neutropenia grade 3, 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Thrombocytopenia grade 3, 1 patient
Disc. AE
400 mg 2 times / day steady, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 22-79 years)
n = 64
Health Status: unhealthy
Condition: Philadelphia chromosome positive chronic myelogenous leukemia - accelerated phase (CML-AP)
Age Group: 59 years (range: 22-79 years)
Sex: M+F
Population Size: 64
Sources:
Neutropenia grade 3-4, 14%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Thrombocytopenia grade 3-4, 17%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Bilirubin total increased grade 3-4, 3%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Conjugated bilirubin level increased grade 3-4, 3%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Fatigue grade 3-4, 3%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Lipase increased grade 3-4, 3%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Rash grade 3-4, 3%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Bilirubin unconjugated increased grade 3-4, 6%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
ALT increased grade 3-4, 9%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
Aspartate aminotransferase increased grade 3-4, 9%
1200 mg 1 times / day steady, oral
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 60 years (range: 15-83 years)
n = 10
Health Status: unhealthy
Condition: Ph-positive ALL | CML
Age Group: 60 years (range: 15-83 years)
Sex: M+F
Population Size: 10
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
weak
yes [IC50 1.7 uM]
yes [Ki 0.132 uM]
yes [Ki 0.19 uM]
yes (pharmacogenomic study)
Comment: The (TA)7/(TA)7 genotype was associated with a statistically significant increase in risk of nilotinib-induced hyperbilirubinemia relative to the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes.
yes [Ki 0.236 uM]
yes [Ki 0.448 uM]
yes (co-administration study)
Comment: nilotinib increased auc of midazolam by 30%
yes [Ki 1.46 uM]
yes [Ki 3.82 uM]
yes
yes
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Beyond imatinib: second generation c-KIT inhibitors for the management of gastrointestinal stromal tumors.
2006 Nov
Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugs.
2007 Apr 15
Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure.
2007 Apr 15
Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders.
2007 Aug
Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability.
2007 Aug
Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor.
2007 Aug 15
Roots of imatinib resistance: a question of self-renewal?
2007 Aug-Oct
Impaired fasting glucose level as metabolic side effect of nilotinib in non-diabetic chronic myeloid leukemia patients resistant to imatinib.
2007 Dec
Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors.
2007 Dec 1
Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets.
2007 Dec 1
What is new in chronic myeloid leukaemia?
2007 Feb
[Innovation of clinical trials for anti-cancer drugs in Japan--proposals from academia with special reference to the development of novel Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406 (NS-187) for imatinib-resistant chronic myelogenous leukemia].
2007 Feb
Important therapeutic targets in chronic myelogenous leukemia.
2007 Feb 15
[Molecular targeting therapy for chronic myeloid leukemia].
2007 Jan
New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.
2007 Jan
Chronic Myeloid Leukaemia in The 21st Century.
2007 Jan
Gateways to clinical trials.
2007 Jan-Feb
Drugs offer new hope for patients with CML who are resistant to imatinib.
2007 Jul
Drug evaluation: Nilotinib - a novel Bcr-Abl tyrosine kinase inhibitor for the treatment of chronic myelocytic leukemia and beyond.
2007 Jul
The tyrosine kinase inhibitor AMN107 (Nilotinib) exhibits off-target effects in lymphoblastic cell lines.
2007 Jul
Monosomy 7 in t(9;22)-negative cells during nilotinib therapy in an imatinib-resistant chronic myeloid leukemia case.
2007 Jul 15
Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity.
2007 Jul 15
BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia.
2007 Jul 19
Gateways to clinical trials.
2007 Jun
[Novel anti-CML agents beyond imatinib].
2007 Jun
Imatinib and nilotinib induce apoptosis of chronic myeloid leukemia cells through a Bim-dependant pathway modulated by cytokines.
2007 Jun
Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells.
2007 Jun
Current and emerging treatment options in chronic myeloid leukemia.
2007 Jun 1
Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study.
2007 Jun 1
High-performance liquid chromatography method with ultraviolet detection for the quantification of the BCR-ABL inhibitor nilotinib (AMN107) in plasma, urine, culture medium and cell preparations.
2007 Jun 1
Gateways to clinical trials.
2007 Mar
Optimal management of patients with newly diagnosed chronic phase chronic myeloid leukemia in 2007.
2007 Mar
Bcr-Abl kinase domain mutations and the unsettled problem of Bcr-AblT315I: looking into the future of controlling drug resistance in chronic myeloid leukemia.
2007 Mar
Emerging safety issues with imatinib and other Abl tyrosine kinase inhibitors.
2007 Mar
Emerging strategies for the treatment of mutant Bcr-Abl T315I myeloid leukemia.
2007 Mar
Resistance to c-KIT kinase inhibitors conferred by V654A mutation.
2007 Mar
Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.
2007 Mar
Gateways to clinical trials.
2007 May
UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.
2007 Nov
Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors.
2007 Nov
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance.
2007 Nov 15
Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells.
2007 Oct
Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia.
2007 Oct 1
How I treat chronic myeloid leukemia in the imatinib era.
2007 Oct 15
Crystal structure of the T315I mutant of AbI kinase.
2007 Sep
Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency.
2007 Sep
The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant bcr/abl+ human leukemia cells in association with signal transducer and activator of transcription 5 inhibition and myeloid cell leukemia-1 down-regulation.
2007 Sep
A critical appraisal of conventional and investigational drug therapy in patients with hypereosinophilic syndrome and clonal eosinophilia.
2007 Sep 1
Tyrosine kinase inhibitors for the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia.
2007 Sep 15
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: The capsules should be swallowed whole with water. No food should be consumed for at least 2 hours before the dose is taken and no food should be consumed for at least one hour after. Dose adjustment may be required for hematologic and non-hematologic toxicities, and drug interactions.
400 mg orally twice daily, approximately 12 hours apart and should not be taken with food.
Route of Administration: Oral
AMN107 (nilotinib) inhibited proliferation of Ba/F3 cells expressing G250E, E255K(V), F317L, M351T, F486S, M244V, L248R, Q252H, Y253H, E255K, E279K, E282D, V289S, and L348M Bcr-Abl mutants at <1 uM concentrations.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:35:16 UTC 2021
Edited
by admin
on Sat Jun 26 03:35:16 UTC 2021
Record UNII
Y37S7HA3BC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NILOTINIB HYDROCHLORIDE DIHYDRATE
Common Name English
BENZAMIDE, 4-METHYL-N-(3-(4-METHYL-1H-IMIDAZOL-1-YL)-5-(TRIFLUOROMETHYL)PHENYL)-3-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINO)-, HYDROCHLORIDE, HYDRATE (1:1:2)
Systematic Name English
Code System Code Type Description
EVMPD
SUB191531
Created by admin on Sat Jun 26 03:35:16 UTC 2021 , Edited by admin on Sat Jun 26 03:35:16 UTC 2021
PRIMARY
FDA UNII
Y37S7HA3BC
Created by admin on Sat Jun 26 03:35:16 UTC 2021 , Edited by admin on Sat Jun 26 03:35:16 UTC 2021
PRIMARY
EPA CompTox
923289-71-8
Created by admin on Sat Jun 26 03:35:16 UTC 2021 , Edited by admin on Sat Jun 26 03:35:16 UTC 2021
PRIMARY
CAS
923289-71-8
Created by admin on Sat Jun 26 03:35:16 UTC 2021 , Edited by admin on Sat Jun 26 03:35:16 UTC 2021
PRIMARY
PUBCHEM
67323320
Created by admin on Sat Jun 26 03:35:16 UTC 2021 , Edited by admin on Sat Jun 26 03:35:16 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY