Identification

Name
Nilotinib
Accession Number
DB04868
Type
Small Molecule
Groups
Approved, Investigational
Description

Nilotinib, also known as AMN107, is a tyrosine kinase inhibitor under investigation as a possible treatment for chronic myelogenous leukemia (CML). In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib (Gleevec®), another tyrosine kinase inhibitor currently used as a first-line treatment. [Wikipedia]

Structure
Thumb
Synonyms
  • Nilotinibum
External IDs
AMN 107 / AMN-107 / AMN107
Product Ingredients
IngredientUNIICASInChI Key
Nilotinib hydrochloride monohydrate5JHU0N1R6K923288-90-8YCBPQSYLYYBPDW-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TasignaCapsule200 mg/1OralNovartis2007-10-29Not applicableUs
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule200 mgOralNovartis2008-09-30Not applicableCanada
TasignaCapsule150 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule50 mg/1OralNovartis2007-10-29Not applicableUs
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
TasignaCapsule200 mgOralNovartis Europharm Limited2007-11-19Not applicableEu
Categories
UNII
F41401512X
CAS number
641571-10-0
Weight
Average: 529.5158
Monoisotopic: 529.183792976
Chemical Formula
C28H22F3N7O
InChI Key
HHZIURLSWUIHRB-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzamide
SMILES
CC1=CN(C=N1)C1=CC(=CC(NC(=O)C2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)=C1)C(F)(F)F

Pharmacology

Indication

For the potential treatment of various leukemias, including chronic myeloid leukemia (CML).

Associated Conditions
Pharmacodynamics

Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML).

Mechanism of action

Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions (Stover et al, 2005; Weisberg et al, 2005). AMN107 also inhibits the c-Kit receptor kinase, including the D816V-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, 2005; von Bubnoff et al, 2005; Gleixner et al, 2006).

TargetActionsOrganism
ATyrosine-protein kinase ABL1
inhibitor
Human
UMast/stem cell growth factor receptor Kit
antagonist
Human
Absorption

Orally available

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

15 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Nilotinib Inhibition of BCR-ABLDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28 or UGT1A 7/7Not Availableextra TA in promoterADR Directly StudiedPatients who carry this polymorphism in UGT1A1 are at a higer risk of developing hyperbilirubinemia when treated with nilotinib.Details

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe therapeutic efficacy of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when used in combination with Nilotinib.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Nilotinib.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Nilotinib.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Nilotinib.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Nilotinib.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Nilotinib.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Nilotinib.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Nilotinib.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Nilotinib.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nilotinib.
Food Interactions
Not Available

References

Synthesis Reference

Yanling WANG, Jie LI, Vinod Kumar KANSAL, Jirang ZHU, Revital LIFSHITZ-LIRON, Dhirenkumar N. MISTRY, Sanjay L. VASOYA, Sundaraselvan ARIYAMUTHU, Gideon PILARSKI, Xungui HE, "NILOTINIB INTERMEDIATES AND PREPARATION THEREOF." U.S. Patent US20100016590, issued January 21, 2010.

US20100016590
General References
  1. Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG: Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. [PubMed:16775235]
  2. Maekawa T, Ashihara E, Kimura S: The Bcr-Abl tyrosine kinase inhibitor imatinib and promising new agents against Philadelphia chromosome-positive leukemias. Int J Clin Oncol. 2007 Oct;12(5):327-40. Epub 2007 Oct 22. [PubMed:17929114]
  3. Breccia M, Cannella L, Nanni M, Stefanizzi C, Alimena G: Nilotinib can override dasatinib resistance in chronic myeloid leukemia patients with secondary resistance to imatinib first-line therapy. Acta Haematol. 2007;118(3):162-4. Epub 2007 Sep 20. [PubMed:17890849]
  4. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, Nicolini FE, O'Brien SG, Litzow M, Bhatia R, Cervantes F, Haque A, Shou Y, Resta DJ, Weitzman A, Hochhaus A, le Coutre P: 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. Blood. 2007 Nov 15;110(10):3540-6. Epub 2007 Aug 22. [PubMed:17715389]
  5. Jabbour E, Cortes J, Giles F, O'Brien S, Kantarijan H: Drug evaluation: Nilotinib - a novel Bcr-Abl tyrosine kinase inhibitor for the treatment of chronic myelocytic leukemia and beyond. IDrugs. 2007 Jul;10(7):468-79. [PubMed:17642017]
External Links
Human Metabolome Database
HMDB0015595
PubChem Compound
644241
PubChem Substance
99443226
ChemSpider
559260
BindingDB
50237710
ChEBI
52172
ChEMBL
CHEMBL255863
PharmGKB
PA165958345
HET
NIL
Wikipedia
Nilotinib
ATC Codes
L01XE08 — Nilotinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3cs9 / 3gp0 / 5mo4
MSDS
Download (68.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentNeurofibromas / Neurofibromatosis / NF11
0Not Yet RecruitingTreatmentChronic Myeloid Leukemia (CML)1
0WithdrawnOtherMalignant Neoplasm of Colon1
1Active Not RecruitingTreatmentChordomas1
1Active Not RecruitingTreatmentChronic Phase Chronic Myeloid Leukemia1
1CompletedNot AvailableChronic Myeloid Leukemia (CML)1
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Myeloid Leukemia (CML)1
1CompletedTreatmentChronic Graft Versus Host Disease1
1CompletedTreatmentChronic Myeloid Leukemia (CML)1
1CompletedTreatmentDiffuse Lewy Body Disease / Parkinson's Disease (PD) / Parkinson's Disease Dementia (PDD)1
1CompletedTreatmentGastrointestinal Stromal Tumors2
1CompletedTreatmentHealthy Volunteers4
1CompletedTreatmentPhiladelphia Chromosome Positive Chronic Myelogenous Leukemia1
1RecruitingTreatmentColorectal Cancers / Head and Neck Carcinoma1
1RecruitingTreatmentChronic Chronic myelogenous leukemia / Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia1
1RecruitingTreatmentRecurrent Low-grade Gliomas / Refractory Low-grade Gliomas1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentLeukemias1
1Unknown StatusTreatmentBone Marrow Transplant Failure / Lymphoma, T-Cell, Peripheral / Non-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentChronic Myeloid Leukemia (CML)1
1, 2CompletedTreatmentAccelerated Phase Chronic Myelogenous Leukemia / Adult Acute Lymphoblastic Leukemia in Remission / Blastic Phase Chronic Myelogenous Leukemia / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Chronic Myelogenous Leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Phase Chronic Myelogenous Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Relapsing Chronic Myelogenous Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
1, 2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Chronic myelogenous leukemia1
1, 2CompletedTreatmentAcute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) / Chronic Chronic myelogenous leukemia / Hypereosinophilic Syndromes / Systemic Mastocytosis1
1, 2CompletedTreatmentAcute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) / Chronic Chronic myelogenous leukemia1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentAccelerated phase chronic myologenic leukemia / Blastic Phase Chronic Myeloid Leukemia / Chronic Phase Chronic Myeloid Leukemia / Philadelphia Positive Acute Lymphoblastic Leukemia / Resistant to Tyrosine Kinase Inhibitor Therapy1
1, 2RecruitingTreatmentChronic Myeloid Leukemia (CML)1
1, 2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1
1, 2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentAdult Acute Lymphoblastic Leukemia in Remission / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Blastic Phase / Blastic Phase Chronic Myelogenous Leukemia / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Phase Chronic Myelogenous Leukemia / Chronic Phase of Disease / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Disease / Relapsing Chronic Myelogenous Leukemia1
2Active Not RecruitingTreatmentBCR-ABL Positive / Bone Marrow Diseases / Dasatinib / Enzyme Inhibitor / Hematologic Diseases / Imatinib / Leukemia, Mylegenous, Accelerated / Leukemia, Mylegenous, Chronic / Leukemia, Myleiod / Leukemias / Myeloproliferative Disorders / Neoplastic Processes / Pediatric Leukemia / Protein Kinase Inhibitors1
2Active Not RecruitingTreatmentCML1
2Active Not RecruitingTreatmentChronic Myeloid Leukemia (CML)3
2Active Not RecruitingTreatmentDiffuse-type Giant Cell Tumor / Synovitis, Pigmented Villonodular / Tenosynovial Giant Cell Tumor1
2Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2Active Not RecruitingTreatmentLeukemia, Myeloid, Chronic-Phase1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentParkinson's Disease (PD) / Parkinsons Disease With Dementia1
2Active Not RecruitingTreatmentPhiladelphia Chromsome Positive Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentTransplantation, Stem Cell / Treatments1
2Active Not RecruitingTreatmentUntreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentChronic Chronic myelogenous leukemia1
2CompletedPreventionMelanoma1
2CompletedPreventionPatients Who Have Received Allo-HSCT1
2CompletedTreatmentAcral Lentiginous Malignant Melanoma / Mucosal Lentiginous Melanoma1
2CompletedTreatmentAcral Melanoma / Melanoma / Mucosal Lentiginous Melanoma1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Myeloid Leukemia (CML) / Transplantation, Stem Cell1
2CompletedTreatmentGastrointestinal Stromal Tumors2
2CompletedTreatmentGastrointestinal Stromal Tumors / Gastrointestinal Stromal Tumors (GISTs)1
2CompletedTreatmentLeukemia, Myelogenous, Chronic1
2CompletedTreatmentLeukemias3
2CompletedTreatmentMetastatic Melanoma With KIT Aberration1
2CompletedTreatmentSclerosis, Progressive Systemic1
2CompletedTreatmentSynovitis, Pigmented Villonodular1
2Not Yet RecruitingTreatmentChronic Chronic myelogenous leukemia / Chronic Myeloid Leukemia (CML) / CML / Hematologic Diseases1
2Not Yet RecruitingTreatmentChronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Minimal Residual Disease1
2RecruitingBasic ScienceChronic Myeloid Leukemia (CML)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Chronic Myelomonocytic Leukemia / Myelodysplastic Syndrome / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Refractory Adult Acute Lymphoblastic Leukemia1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentChronic Myeloid Leukemia (CML)1
2RecruitingTreatmentChronic Chronic myelogenous leukemia / Chronic Myeloid Leukemia (CML) / Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Leukemias1
2RecruitingTreatmentChronic Myeloid Leukemia in Myeloid Blast Crisis / Untreated Adult Acute Myeloid Leukemia1
2RecruitingTreatmentChronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive1
2RecruitingTreatmentGliomas1
2RecruitingTreatmentLeukemia, Myelogenous, Chronic, BCR-ABL Positive1
2RecruitingTreatmentMalignant Solid Neoplasms1
2RecruitingTreatmentRecurrent Low-grade Gliomas / Refractory Low-grade Gliomas1
2TerminatedTreatmentGIST / Metastatic Disease1
2TerminatedTreatmentGastrointestinal Stromal Tumors1
2TerminatedTreatmentGrowing Vestibular Schwannomas1
2TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
2Unknown StatusNot AvailableChronic Myeloid Leukemia (CML)1
2Unknown StatusTreatmentAmplification / Malignant Skin Melanoma T0 / Stage III Melanoma / Stage IV Melanoma1
2Unknown StatusTreatmentChronic Myeloid Leukemia (CML)1
2WithdrawnTreatmentB-cell Adult Acute Lymphoblastic Leukemia / Blastic Phase Chronic Myelogenous Leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia1
2WithdrawnTreatmentGastrointestinal Cancers1
2, 3CompletedTreatmentChronic Myeloid Leukemia (CML)1
3Active Not RecruitingDiagnosticChronic Myeloid Leukemia (CML)1
3Active Not RecruitingTreatmentChronic Phase Chronic Myeloid Leukemia1
3Active Not RecruitingTreatmentChronic Chronic myelogenous leukemia1
3Approved for MarketingNot AvailableChronic Myeloid Leukemia (CML)1
3CompletedTreatmentChronic Myeloid Leukemia (CML)4
3CompletedTreatmentGastrointestinal Stromal Tumors2
3CompletedTreatmentGastrointestinal Stromal Tumors (GISTs)1
3CompletedTreatmentLeukemia, Myeloid, Chronic, BCR-ABL Positive1
3CompletedTreatmentLeukemias1
3CompletedTreatmentPhiladelphia Positive (Ph+) Chronic Myeloid Leukemia1
3CompletedTreatmentChronic Chronic myelogenous leukemia2
3No Longer AvailableNot AvailableChronic Myeloid Leukemia (CML)1
3No Longer AvailableNot AvailableChronic Chronic myelogenous leukemia1
3RecruitingTreatmentChronic Myeloid Leukemia (CML)2
3RecruitingTreatmentChronic Myeloid Leukemia - Chronic Phase1
3RecruitingTreatmentLeukemia, Myeloid, Ph1-Positive1
3RecruitingTreatmentPhiladelphia Chromosome Positive Adult Acute Lymphoblastic Leukemia1
3RecruitingTreatmentChronic Chronic myelogenous leukemia1
3SuspendedTreatmentChronic Myeloid Leukemia (CML)1
3TerminatedTreatmentGastrointestinal Stromal Tumors1
3TerminatedTreatmentMyelogenous Leukemia1
3TerminatedTreatmentPhilidelphia Positive Chronic Myeloid Leukaemia1
3Unknown StatusTreatmentChronic Myeloid Leukemia (CML)1
4Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
4CompletedTreatmentCML / Imatinib Intolerant / Imatinib Resistant / Nilotinib1
4CompletedTreatmentChronic Myelogenous Leukemia - Chronic Phase1
4CompletedTreatmentChronic Myelogenous Leukemia in Chronic Phase1
4CompletedTreatmentChronic Myelogenous Leukemia in Chronic Phase / Philadelphia Chromosome Positive1
4CompletedTreatmentChronic Myeloid Leukemia (CML)1
4CompletedTreatmentChronic Myeloid Leukemia, Chronic Phase1
4CompletedTreatmentMyeloid Leukemias1
4CompletedTreatmentChronic Chronic myelogenous leukemia2
4Not Yet RecruitingTreatmentChronic Myeloid Leukemia (CML)1
4RecruitingTreatmentChronic Myeloid Leukemia (CML)1
4RecruitingTreatmentChronyc Myeloid Leukemia1
4RecruitingTreatmentGIST and CML1
4TerminatedTreatmentChronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels / CML / Philadelphia Chromosome Positive (Ph+)1
4TerminatedTreatmentChronic Myeloid Leukemia (CML)1
4WithdrawnTreatmentChronic Myeloid Leukemia (CML)1
Not AvailableCompletedNot AvailableAll Indications for Glivec/Gleevec and Tasigna1
Not AvailableCompletedNot AvailableChronic Myeloid Leukemia (CML)1
Not AvailableCompletedNot AvailableGastrointestinal Stromal Tumors1
Not AvailableRecruitingNot AvailableAcute Lymphoblastic Leukaemias (ALL)1
Not AvailableRecruitingTreatmentChronic Chronic myelogenous leukemia1
Not AvailableUnknown StatusNot AvailableChronic Myeloid Leukemia (CML)1
Not AvailableWithdrawnNot AvailableLeukemia, Myelogenous, Chronic, BCR-ABL Positive1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral150 mg/1
CapsuleOral150 mg
CapsuleOral200 mg
CapsuleOral200 mg/1
CapsuleOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2491632No2009-11-102023-07-04Canada
US7169791Yes2004-01-042024-01-04Us
US8389537Yes2007-01-182027-01-18Us
US8415363Yes2007-01-182027-01-18Us
US8293756Yes2008-03-252028-03-25Us
US8501760Yes2007-01-182027-01-18Us
US8163904Yes2009-02-232029-02-23Us
US9061029Yes2012-10-072032-10-07Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00201 mg/mLALOGPS
logP4.51ALOGPS
logP4.41ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)11.86ChemAxon
pKa (Strongest Basic)6.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.62 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity152.85 m3·mol-1ChemAxon
Polarizability52.35 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9066
Caco-2 permeable-0.5792
P-glycoprotein substrateNon-substrate0.6879
P-glycoprotein inhibitor IInhibitor0.556
P-glycoprotein inhibitor IIInhibitor0.6002
Renal organic cation transporterNon-inhibitor0.8253
CYP450 2C9 substrateNon-substrate0.8178
CYP450 2D6 substrateNon-substrate0.8547
CYP450 3A4 substrateSubstrate0.5552
CYP450 1A2 substrateInhibitor0.7324
CYP450 2C9 inhibitorNon-inhibitor0.5739
CYP450 2D6 inhibitorNon-inhibitor0.8275
CYP450 2C19 inhibitorInhibitor0.5554
CYP450 3A4 inhibitorInhibitor0.6784
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7862
Ames testNon AMES toxic0.5204
CarcinogenicityNon-carcinogens0.8175
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6343 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9961
hERG inhibition (predictor II)Inhibitor0.8458
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0000090000-c81d93ae83b54aaca2f4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0000090000-2a5b68b4c129b14bb357
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0090010000-4d81b7c6e95b1601807c
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0290000000-5cdcf0a130834a5ce0fa
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-006x-1980000000-fe1aac1a4cf8b0cf243f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0089-4920000000-41fd6570440f9acb13a2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-9300000000-3dde52b181ab459e7373
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-9000000000-2fbed5a3e77fb33d74f6
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0gc1-9000000000-8d60ba6c0beff21b5ceb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0000090000-ad94cdcfe3b41c7e6e1c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053i-0095050000-60d1fbdd2ffcd3cc7cb3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-08fr-0091000000-0b24555ab7c56e04ca80
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-08fr-0090000000-dac0910c08fc1e3b20b1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0190000000-5cc32e0bf9ad1cbe4ae8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0390000000-7834bc808d80c86e0918
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4l-3890000000-c8db809bdbc2f49eb4db
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a6v-6940000000-2febde67f881b42dd11e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0h0a-9720000000-5868b8d3e3c7531fdfcd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0181090000-fac2f8f712c3e67b317e

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Pyridinylpyrimidines / Phenylimidazoles / Trifluoromethylbenzenes / Aminobenzoic acids and derivatives / p-Toluamides / Benzamides / Aniline and substituted anilines / Benzoyl derivatives / Aminopyrimidines and derivatives / Pyridines and derivatives
show 12 more
Substituents
Benzanilide / Pyridinylpyrimidine / 1-phenylimidazole / Trifluoromethylbenzene / Aminobenzoic acid or derivatives / P-toluamide / Toluamide / Benzamide / Benzoic acid or derivatives / Benzoyl
show 29 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, pyrimidines, secondary amino compound, pyridines, carboxamide, (trifluoromethyl)benzenes (CHEBI:52172)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
References
  1. Maekawa T, Ashihara E, Kimura S: The Bcr-Abl tyrosine kinase inhibitor imatinib and promising new agents against Philadelphia chromosome-positive leukemias. Int J Clin Oncol. 2007 Oct;12(5):327-40. Epub 2007 Oct 22. [PubMed:17929114]
  2. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, Nicolini FE, O'Brien SG, Litzow M, Bhatia R, Cervantes F, Haque A, Shou Y, Resta DJ, Weitzman A, Hochhaus A, le Coutre P: 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. Blood. 2007 Nov 15;110(10):3540-6. Epub 2007 Aug 22. [PubMed:17715389]
  3. Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD: AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br J Cancer. 2006 Jun 19;94(12):1765-9. Epub 2006 May 23. [PubMed:16721371]
  4. Swords R, Mahalingam D, Padmanabhan S, Carew J, Giles F: Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. Drug Des Devel Ther. 2009 Sep 21;3:89-101. [PubMed:19920925]
  5. Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M: Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12. [PubMed:19822896]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Guo T, Agaram NP, Wong GC, Hom G, D'Adamo D, Maki RG, Schwartz GK, Veach D, Clarkson BD, Singer S, DeMatteo RP, Besmer P, Antonescu CR: Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res. 2007 Aug 15;13(16):4874-81. [PubMed:17699867]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Tanaka C, Yin OQ, Smith T, Sethuraman V, Grouss K, Galitz L, Harrell R, Schran H: Effects of rifampin and ketoconazole on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol. 2011 Jan;51(1):75-83. doi: 10.1177/0091270010367428. Epub 2010 Aug 11. [PubMed:20702754]
  2. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
  3. Yin OQ, Gallagher N, Tanaka C, Fisher D, Sethuraman V, Zhou W, Lin TH, Heuman D, Schran H: Effects of hepatic impairment on the pharmacokinetics of nilotinib: an open-label, single-dose, parallel-group study. Clin Ther. 2009;31 Pt 2:2459-69. doi: 10.1016/j.clinthera.2009.11.015. [PubMed:20110053]
  4. Deremer DL, Ustun C, Natarajan K: Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin Ther. 2008 Nov;30(11):1956-75. doi: 10.1016/j.clinthera.2008.11.014. [PubMed:19108785]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
  2. Deremer DL, Ustun C, Natarajan K: Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin Ther. 2008 Nov;30(11):1956-75. doi: 10.1016/j.clinthera.2008.11.014. [PubMed:19108785]
  3. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Yin OQ, Gallagher N, Fischer D, Zhao L, Zhou W, Leroy E, Golor G, Schran H: Effects of nilotinib on single-dose warfarin pharmacokinetics and pharmacodynamics: a randomized, single-blind, two-period crossover study in healthy subjects. Clin Drug Investig. 2011;31(3):169-79. doi: 10.2165/11538700-000000000-00000. [PubMed:21184622]
  2. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
  2. Deremer DL, Ustun C, Natarajan K: Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin Ther. 2008 Nov;30(11):1956-75. doi: 10.1016/j.clinthera.2008.11.014. [PubMed:19108785]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995]
  2. Hegedus C, Ozvegy-Laczka C, Apati A, Magocsi M, Nemet K, Orfi L, Keri G, Katona M, Takats Z, Varadi A, Szakacs G, Sarkadi B: Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662]
  3. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995]
  2. Hegedus C, Ozvegy-Laczka C, Apati A, Magocsi M, Nemet K, Orfi L, Keri G, Katona M, Takats Z, Varadi A, Szakacs G, Sarkadi B: Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662]
  3. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87. doi: 10.1182/blood-2010-07-294330. Epub 2010 Sep 1. [PubMed:20810928]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A: Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014 Feb 18;110(4):894-8. doi: 10.1038/bjc.2013.811. Epub 2014 Jan 7. [PubMed:24398510]

Drug created on October 20, 2007 03:39 / Updated on September 21, 2018 00:12