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Identification
NameNilotinib
Accession NumberDB04868
TypeSmall Molecule
GroupsApproved, 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 Identifiers
  • AMN 107
  • AMN-107
  • AMN107
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tasignacapsule200 mg/1oralNovartis Pharmaceuticals Corporation2007-10-29Not applicableUs
Tasignacapsule150 mgoralNovartis Pharmaceuticals Canada Inc2011-07-15Not applicableCanada
Tasignacapsule200 mgoralNovartis Pharmaceuticals Canada Inc2008-09-30Not applicableCanada
Tasignacapsule150 mg/1oralNovartis Pharmaceuticals Corporation2007-10-29Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Nilotinib hydrochloride monohydrate
ThumbNot applicableDBSALT001325
Categories
UNIIF41401512X
CAS number641571-10-0
WeightAverage: 529.5158
Monoisotopic: 529.183792976
Chemical FormulaC28H22F3N7O
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-phenylbenzamides. These are benzamides that are N-linked to a phenyl group via the carboxamide group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-phenylbenzamides
Alternative Parents
Substituents
  • N-phenylbenzamide
  • Pyridinylpyrimidine
  • 1-phenylimidazole
  • N-arylamide
  • Aminobenzoic acid or derivatives
  • Benzoic acid or derivatives
  • Aminotoluene
  • Benzoyl
  • Toluene
  • Pyrimidine
  • Pyridine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the potential treatment of various leukemias, including chronic myeloid leukemia (CML).
PharmacodynamicsNilotinib 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 actionChronic 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).
Related Articles
AbsorptionOrally available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life15 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral150 mg
Capsuleoral150 mg/1
Capsuleoral200 mg/1
Capsuleoral200 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2491632 No2009-11-102023-07-04Canada
US7169791 No2003-07-042023-07-04Us
US8163904 No2008-08-232028-08-23Us
US8293756 No2007-09-252027-09-25Us
US8389537 No2006-07-182026-07-18Us
US8415363 No2006-07-182026-07-18Us
US8501760 No2006-07-182026-07-18Us
Properties
StateSolid
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot 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
ATC CodesL01XE08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (68.9 KB)
Interactions
Drug Interactions
Drug
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nilotinib.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Nilotinib.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Nilotinib.
Aluminum hydroxideThe serum concentration of Nilotinib can be decreased when it is combined with Aluminum hydroxide.
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Nilotinib.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Nilotinib.
AprepitantThe serum concentration of Nilotinib can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Nilotinib can be increased when it is combined with Atazanavir.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Nilotinib.
BexaroteneThe serum concentration of Nilotinib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Nilotinib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Nilotinib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Nilotinib.
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Nilotinib.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Nilotinib.
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Nilotinib.
Calcium carbonateThe serum concentration of Nilotinib can be decreased when it is combined with Calcium carbonate.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Nilotinib.
CarbamazepineThe serum concentration of Nilotinib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Nilotinib can be increased when it is combined with Ceritinib.
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Nilotinib.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Nilotinib.
CimetidineThe serum concentration of Nilotinib can be decreased when it is combined with Cimetidine.
CitalopramCitalopram may increase the QTc-prolonging activities of Nilotinib.
ClarithromycinThe serum concentration of Nilotinib can be increased when it is combined with Clarithromycin.
ClozapineThe risk or severity of adverse effects can be increased when Nilotinib is combined with Clozapine.
CobicistatThe serum concentration of Nilotinib can be increased when it is combined with Cobicistat.
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Nilotinib.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Nilotinib.
ConivaptanThe serum concentration of Nilotinib can be increased when it is combined with Conivaptan.
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Nilotinib.
DabrafenibThe serum concentration of Nilotinib can be decreased when it is combined with Dabrafenib.
DapoxetineThe serum concentration of Dapoxetine can be increased when it is combined with Nilotinib.
DarunavirThe serum concentration of Nilotinib can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Nilotinib can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Nilotinib.
DexamethasoneThe serum concentration of Nilotinib can be decreased when it is combined with Dexamethasone.
DofetilideDofetilide may increase the QTc-prolonging activities of Nilotinib.
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Nilotinib.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Nilotinib.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Nilotinib.
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Nilotinib.
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Nilotinib.
EnzalutamideThe serum concentration of Nilotinib can be decreased when it is combined with Enzalutamide.
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Nilotinib.
EsomeprazoleThe serum concentration of Nilotinib can be decreased when it is combined with Esomeprazole.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Nilotinib.
FamotidineThe serum concentration of Nilotinib can be decreased when it is combined with Famotidine.
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Nilotinib.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Nilotinib.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Nilotinib.
FluconazoleThe metabolism of Nilotinib can be decreased when combined with Fluconazole.
FlunisolideThe metabolism of Flunisolide can be decreased when combined with Nilotinib.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Nilotinib.
FosaprepitantThe serum concentration of Nilotinib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Nilotinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Nilotinib can be increased when it is combined with Fusidic Acid.
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Nilotinib.
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Nilotinib.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Nilotinib.
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Nilotinib.
GoserelinGoserelin may increase the QTc-prolonging activities of Nilotinib.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Nilotinib.
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Nilotinib.
IdelalisibThe serum concentration of Nilotinib can be increased when it is combined with Idelalisib.
IfosfamideThe serum concentration of the active metabolites of Ifosfamide can be reduced when Ifosfamide is used in combination with Nilotinib resulting in a loss in efficacy.
ImatinibThe serum concentration of Imatinib can be increased when it is combined with Nilotinib.
IndinavirThe serum concentration of Nilotinib can be increased when it is combined with Indinavir.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Nilotinib.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Nilotinib.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Nilotinib.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Nilotinib.
Insulin HumanThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Nilotinib.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Nilotinib.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Nilotinib.
ItraconazoleThe serum concentration of Nilotinib can be increased when it is combined with Itraconazole.
IvabradineThe serum concentration of Ivabradine can be increased when it is combined with Nilotinib.
IvacaftorThe serum concentration of Ivacaftor can be increased when it is combined with Nilotinib.
KetoconazoleThe serum concentration of Nilotinib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Nilotinib can be decreased when it is combined with Lansoprazole.
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Nilotinib.
LeflunomideThe risk or severity of adverse effects can be increased when Nilotinib is combined with Leflunomide.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Nilotinib.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Nilotinib.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Nilotinib.
LuliconazoleThe serum concentration of Nilotinib can be increased when it is combined with Luliconazole.
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Nilotinib.
Magnesium hydroxideThe serum concentration of Nilotinib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Nilotinib can be decreased when it is combined with Magnesium oxide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Nilotinib.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Nilotinib.
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Nilotinib.
MifepristoneMifepristone may increase the QTc-prolonging activities of Nilotinib.
MitotaneThe serum concentration of Nilotinib can be decreased when it is combined with Mitotane.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Nilotinib.
NatalizumabThe risk or severity of adverse effects can be increased when Nilotinib is combined with Natalizumab.
NebivololThe serum concentration of Nebivolol can be increased when it is combined with Nilotinib.
NefazodoneThe serum concentration of Nilotinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Nilotinib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Nilotinib can be increased when it is combined with Netupitant.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Nilotinib.
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Nilotinib.
NizatidineThe serum concentration of Nilotinib can be decreased when it is combined with Nizatidine.
OctreotideOctreotide may increase the QTc-prolonging activities of Nilotinib.
OlaparibThe serum concentration of Olaparib can be increased when it is combined with Nilotinib.
OmeprazoleThe serum concentration of Nilotinib can be decreased when it is combined with Omeprazole.
OxycodoneThe risk or severity of adverse effects can be increased when Nilotinib is combined with Oxycodone.
PalbociclibThe serum concentration of Nilotinib can be increased when it is combined with Palbociclib.
PantoprazoleThe serum concentration of Nilotinib can be decreased when it is combined with Pantoprazole.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Nilotinib.
PhenobarbitalThe serum concentration of Nilotinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Nilotinib can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Nilotinib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Nilotinib.
PosaconazoleThe serum concentration of Nilotinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Nilotinib can be decreased when it is combined with Primidone.
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Nilotinib.
RabeprazoleThe serum concentration of Nilotinib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Nilotinib can be decreased when it is combined with Ranitidine.
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Nilotinib.
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Nilotinib.
RifabutinThe serum concentration of Nilotinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Nilotinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Nilotinib can be decreased when it is combined with Rifapentine.
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Nilotinib.
RitonavirThe serum concentration of Nilotinib can be increased when it is combined with Ritonavir.
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Nilotinib.
RoflumilastRoflumilast may increase the immunosuppressive activities of Nilotinib.
SaquinavirThe serum concentration of Nilotinib can be increased when it is combined with Saquinavir.
SaxagliptinThe serum concentration of Saxagliptin can be increased when it is combined with Nilotinib.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Nilotinib.
SiltuximabThe serum concentration of Nilotinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Nilotinib.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Nilotinib.
Sodium bicarbonateThe serum concentration of Nilotinib can be decreased when it is combined with Sodium bicarbonate.
SonidegibThe serum concentration of Sonidegib can be increased when it is combined with Nilotinib.
St. John's WortThe serum concentration of Nilotinib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Nilotinib can be increased when it is combined with Stiripentol.
SuvorexantThe serum concentration of Suvorexant can be increased when it is combined with Nilotinib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Nilotinib.
TamoxifenThe serum concentration of the active metabolites of Tamoxifen can be reduced when Tamoxifen is used in combination with Nilotinib resulting in a loss in efficacy.
TelaprevirThe serum concentration of Nilotinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Nilotinib can be increased when it is combined with Telithromycin.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Nilotinib.
TocilizumabThe serum concentration of Nilotinib can be decreased when it is combined with Tocilizumab.
TofacitinibNilotinib may increase the immunosuppressive activities of Tofacitinib.
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Nilotinib.
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Nilotinib.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Nilotinib.
TorasemideThe metabolism of Torasemide can be decreased when combined with Nilotinib.
TrabectedinThe serum concentration of Trabectedin can be increased when it is combined with Nilotinib.
TramadolThe therapeutic efficacy of Tramadol can be decreased when used in combination with Nilotinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Nilotinib.
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Nilotinib.
VerapamilThe serum concentration of Verapamil can be increased when it is combined with Nilotinib.
VilazodoneThe serum concentration of Vilazodone can be increased when it is combined with Nilotinib.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Nilotinib.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Nilotinib.
VindesineThe serum concentration of Vindesine can be increased when it is combined with Nilotinib.
VoriconazoleThe serum concentration of Nilotinib can be increased when it is combined with Voriconazole.
ZopicloneThe serum concentration of Zopiclone can be increased when it is combined with Nilotinib.
Food InteractionsNot Available

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 and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 ...
Gene Name:
ABL1
Uniprot ID:
P00519
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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
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
substrateinhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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
substrateinhibitor
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
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
substrateinhibitor
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
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 IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
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 ]
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Drug created on October 20, 2007 03:39 / Updated on May 29, 2016 02:11