Nilotinib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H22F3N7O
Molecular Weight	529.5158
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CN(C=N1)C2=CC(NC(=O)C3=CC=C(C)C(NC4=NC=CC(=N4)C5=CN=CC=C5)=C3)=CC(=C2)C(F)(F)F

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	529.5158
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022068lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bcr/Abl fusion protein 21 Target ID: CHEMBL2096618 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19920925	Inhibitor 8504		0.33 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022068s023lbl.pdf	Primary		Approved 8583	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 2007

C_max

Value	Dose	Analyte	Population
405.111 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
402.715 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
1550 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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
2490 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2190 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
403 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1360 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30179260	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30179260	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

Value	Dose	Analyte	Population
4160.969 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
2795.782 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
15129.182 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
14383.076 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01077544	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:
12700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19924121	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
28000 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26600 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4480 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11865 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30179260	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30179260	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

F_unbound

Value	Dose	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILOTINIB serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.6% OTHER GOV https://www.ema.europa.eu/en/documents/scientific-discussion/tasigna-epar-scientific-discussion_en.pdf		NILOTINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf	unhealthy, 56 years (range: 26-85 years) Health Status: unhealthy Age Group: 56 years (range: 26-85 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf
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: https://pubmed.ncbi.nlm.nih.gov/19924121/	unhealthy, 56.2 ± 15.3 years Health Status: unhealthy Age Group: 56.2 ± 15.3 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19924121/	Sources: https://pubmed.ncbi.nlm.nih.gov/19924121/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf	unhealthy, 59 years (range: 22-79 years) Health Status: unhealthy Age Group: 59 years (range: 22-79 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_MedR_P2.pdf
1200 mg 1 times / day steady, oral Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf https://pubmed.ncbi.nlm.nih.gov/16775235	unhealthy, 60 years (range: 15-83 years) Health Status: unhealthy Age Group: 60 years (range: 15-83 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf https://pubmed.ncbi.nlm.nih.gov/16775235	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf https://pubmed.ncbi.nlm.nih.gov/16775235

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 substrate 1946	inducer 440 inhibitor 2438 substrate 1193	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A4/5 296 CYP2C8 1057 CYP2C19 2057 P-gp 1741 UGT1A1 246	P-gp 2052 MRP1 113 CYP2J2 71 CYP1A2 1197 CYP2C8 810 OCT1 393	CYP2B6 669 CYP2C8 198 CYP1A1 151 CYP1A2 832 UGT1A1 78 CYP2C19 329 P-gp 301 MRP2 146

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	no
MRP2 625	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	no
P-gp 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	no
UGT1A1 303	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	weak
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [IC50 1.7 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [Ki 0.132 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [Ki 0.236 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [Ki 0.448 uM]	yes (co-administration study) Comment: nilotinib increased auc of midazolam by 30% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [Ki 1.46 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes [Ki 3.82 uM]
CYP1A1 272	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	major	yes (co-administration study) Comment: ketoconazole increased auc of nilotinib by 3x, cmax by 84% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	minor
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	minor
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	minor
CYP2J2 71	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	minor
MRP1 113	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022068s000_PharmR_P1.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:52172	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:52172
ChemicalBook	CB5966228	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5966228
eMolecules	10645209	https://www.emolecules.com/cgi-bin/more?vid=10645209
MolPort	MolPort-003-987-089	https://www.molport.com/shop/molecule-link/MolPort-003-987-089
Selleck Chemicals	Nilotinib	http://www.selleckchem.com/products/Nilotinib.html
ZINC	ZINC000006716957	http://zinc15.docking.org/substances/ZINC000006716957

PubMed

Title	Date	PubMed
Novel treatment strategies for chronic myeloid leukemia.	2006 Dec 1	17106016
Beyond imatinib: second generation c-KIT inhibitors for the management of gastrointestinal stromal tumors.	2006 Nov	17419150
Gateways to clinical trials.	2006 Oct	17136234
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	17110460
Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugs.	2007 Apr 15	17409347
Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure.	2007 Apr 15	17342766
Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders.	2007 Aug	17691909
Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability.	2007 Aug	17614824
Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor.	2007 Aug 15	17699867
Roots of imatinib resistance: a question of self-renewal?	2007 Aug-Oct	17683977
Impaired fasting glucose level as metabolic side effect of nilotinib in non-diabetic chronic myeloid leukemia patients resistant to imatinib.	2007 Dec	17382388
Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors.	2007 Dec 1	17785585
Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets.	2007 Dec 1	17720881
What is new in chronic myeloid leukaemia?	2007 Feb	17373424
Important therapeutic targets in chronic myelogenous leukemia.	2007 Feb 15	17317816
New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.	2007 Jan	17292738
Chronic Myeloid Leukaemia in The 21st Century.	2007 Jan	17288299
Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia.	2007 Jan	17164530
Gateways to clinical trials.	2007 Jan-Feb	17344945
Drugs offer new hope for patients with CML who are resistant to imatinib.	2007 Jul	17694781
Drug evaluation: Nilotinib - a novel Bcr-Abl tyrosine kinase inhibitor for the treatment of chronic myelocytic leukemia and beyond.	2007 Jul	17642017
The tyrosine kinase inhibitor AMN107 (Nilotinib) exhibits off-target effects in lymphoblastic cell lines.	2007 Jul	17613767
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	17450179
Monosomy 7 in t(9;22)-negative cells during nilotinib therapy in an imatinib-resistant chronic myeloid leukemia case.	2007 Jul 15	17656263
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	17559140
BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia.	2007 Jul 19	17634461
Gateways to clinical trials.	2007 Jun	17805439
[Novel anti-CML agents beyond imatinib].	2007 Jun	17633095
Imatinib and nilotinib induce apoptosis of chronic myeloid leukemia cells through a Bim-dependant pathway modulated by cytokines.	2007 Jun	17538248
Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells.	2007 Jun	17519960
Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study.	2007 Jun 1	17303698
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	17291840
Gateways to clinical trials.	2007 Mar	17440629
Emerging safety issues with imatinib and other Abl tyrosine kinase inhibitors.	2007 Mar	17382019
Emerging strategies for the treatment of mutant Bcr-Abl T315I myeloid leukemia.	2007 Mar	17382017
Resistance to c-KIT kinase inhibitors conferred by V654A mutation.	2007 Mar	17363509
Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.	2007 Mar	17355221
Gateways to clinical trials.	2007 May	17609744
Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells.	2007 May 1	17213283
UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.	2007 Nov	17611564
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	17403535
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	17715389
Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells.	2007 Oct	17681669
Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia.	2007 Oct 1	17496200
How I treat chronic myeloid leukemia in the imatinib era.	2007 Oct 15	17626839
Crystal structure of the T315I mutant of AbI kinase.	2007 Sep	17718712
Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency.	2007 Sep	17710227
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	17595328
A critical appraisal of conventional and investigational drug therapy in patients with hypereosinophilic syndrome and clonal eosinophilia.	2007 Sep 1	17654661
Tyrosine kinase inhibitors for the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia.	2007 Sep 15	17701954

Patents

Sample Use Guides

In Vivo Use Guide

400 mg orally twice daily, approximately 12 hours apart and should not be taken with food.

Route of Administration: Oral

In Vitro Use Guide

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 `Mon Mar 31 18:26:45 GMT 2025` Edited by `admin` on `Mon Mar 31 18:26:45 GMT 2025`
Record UNII	F41401512X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Nilotinib

Official Name

English

AMN107

Preferred 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 [USP-RS]

Common Name

English

4-Methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzamide

Systematic Name

English

NILOTINIB [MART.]

Common Name

English

Nilotinib [WHO-DD]

Common Name

English

NSC-747599

Code

English

AMN-107

Code

English

NILOTINIB [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

786820