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

Details

Stereochemistry ACHIRAL
Molecular Formula C28H22F3N7O
Molecular Weight 529.5168
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NILOTINIB

SMILES

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

InChI

InChIKey=HHZIURLSWUIHRB-UHFFFAOYSA-N
InChI=1S/C28H22F3N7O/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)

HIDE SMILES / InChI

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
Tyrosine kinase inhibitors: the next generation.
2006 Aug
American Society of Clinical Oncology--42nd annual meeting. Poster presentations on leukemia and cytotoxic chemotherapy. 2-6 June 2006, Atlanta, GA, USA.
2006 Aug
Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107).
2006 Aug 15
Gateways to clinical trials.
2006 Dec
Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-alpha-expressing cells.
2006 Dec
Novel treatment strategies for chronic myeloid leukemia.
2006 Dec 1
Activity of AMN107 in gleevec-resistant leukemia.
2006 Jan
OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib.
2006 Jul 15
Combined effects of novel tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl-expressing human leukemia cells.
2006 Jul 15
Circumventing resistance to kinase-inhibitor therapy.
2006 Jun 15
Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.
2006 Jun 15
The FIP1L1-PDGFRA T674I mutation can be inhibited by the tyrosine kinase inhibitor AMN107 (nilotinib).
2006 Jun 15
Kinase inhibitors in chronic myelogenous leukemia.
2006 May
Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.
2006 Nov
Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human mast cells bearing wild-type or mutated codon 816 c-kit.
2006 Nov
The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells.
2006 Nov 15
Gateways to clinical trials.
2006 Oct
Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations.
2006 Oct 1
Identification of MCL1 as a novel target in neoplastic mast cells in systemic mastocytosis: inhibition of mast cell survival by MCL1 antisense oligonucleotides and synergism with PKC412.
2007 Apr 1
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
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
KIT mutations in GIST.
2007 Feb
Simultaneous determination of AMN107 and Imatinib (Gleevec, Glivec, STI571) in cultured tumour cells using an isocratic high-performance liquid chromatography procedure with UV detection.
2007 Feb 1
[Molecular targeting therapy for chronic myeloid leukemia].
2007 Jan
Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia.
2007 Jan
MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation.
2007 Jan 15
Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure.
2007 Jan 15
Gateways to clinical trials.
2007 Jan-Feb
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
Successful allogeneic stem cell transplantation in second chronic-phase CML induced by the tyrosine kinase inhibitor nilotinib (AMN107) after blast crisis under imatinib.
2007 Jul
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
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
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
Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation.
2007 Mar 1
Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias.
2007 Mar 1
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
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 Fri Jun 25 21:23:33 UTC 2021
Edited
by admin
on Fri Jun 25 21:23:33 UTC 2021
Record UNII
F41401512X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NILOTINIB
DASH   EMA EPAR   HSDB   INN   MART.   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
NILOTINIB [USAN]
Common Name English
NILOTINIB [EMA EPAR]
Common Name English
NILOTINIB [VANDF]
Common Name English
BENZAMIDE, 4-METHYL-N-(3-(4-METHYL-1H-IMIDAZOL-1-YL)-5-(TRIFLUOROMETHYL)PHENYL)-3-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINO)-
Systematic Name English
NILOTINIB [HSDB]
Common Name English
NILOTINIB [INN]
Common Name English
NILOTINIB [WHO-DD]
Common Name English
AMN107
Code English
NILOTINIB [USP-RS]
Common Name English
4-METHYL-N-(3-(4-METHYL-1H-IMIDAZOL-1-YL)-5-(TRIFLUOROMETHYL)PHENYL)-3-((4-PYRIDIN-3-YLPYRIMIDIN-2-YL)AMINO)BENZAMIDE
Systematic Name English
NILOTINIB [MART.]
Common Name English
AMN 107
Code English
NSC-747599
Code English
AMN-107
Code English
NILOTINIB [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 786820
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
FDA ORPHAN DRUG 788520
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
FDA ORPHAN DRUG 743720
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
WHO-ATC L01XE08
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
LIVERTOX 685
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
FDA ORPHAN DRUG 237307
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
NDF-RT N0000175076
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
WHO-VATC QL01XE08
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
EU-Orphan Drug EU/3/06/375
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
NCI_THESAURUS C155700
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
EMA ASSESSMENT REPORTS TASIGNA ( AUTHORIZED: LEUKEMIA , MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
FDA ORPHAN DRUG 220806
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
Code System Code Type Description
DRUG CENTRAL
1932
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
IUPHAR
5697
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
DRUG BANK
DB04868
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
LACTMED
Nilotinib
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
ChEMBL
CHEMBL255863
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
INN
8654
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
USP_CATALOG
1463428
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY USP-RS
FDA UNII
F41401512X
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
HSDB
7842
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
EVMPD
SUB25225
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
RXCUI
662281
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY RxNorm
CAS
641571-10-0
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
PUBCHEM
644241
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
EPA CompTox
641571-10-0
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
NCI_THESAURUS
C48375
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
MERCK INDEX
M11754
Created by admin on Fri Jun 25 21:23:33 UTC 2021 , Edited by admin on Fri Jun 25 21:23:33 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
SALT/SOLVATE -> PARENT
RESISTANT TARGET->INHIBITOR
TARGET -> INHIBITOR
INHIBITOR
TRANSPORTER -> SUBSTRATE
RESISTANT TARGET->INHIBITOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
FECAL
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
FECAL
Related Record Type Details
ACTIVE MOIETY