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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
SynonymLanguageCode
AMN 107Not AvailableNot Available
AMN-107Not AvailableNot Available
AMN107Not AvailableNot Available
NilotinibumNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tasignacapsule200 mgoralNovartis Pharmaceuticals Corporation2007-10-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tasignacapsule150 mgoralNovartis Pharmaceuticals Corporation2007-10-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tasignacapsule200 mgoralNovartis Pharmaceuticals Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tasignacapsule150 mgoralNovartis Pharmaceuticals Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number641571-10-0
WeightAverage: 529.5158
Monoisotopic: 529.183792976
Chemical FormulaC28H22F3N7O
InChI KeyHHZIURLSWUIHRB-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).
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 substrateNon-inhibitor0.5739
CYP450 2D6 substrateNon-inhibitor0.8275
CYP450 2C19 substrateInhibitor0.5554
CYP450 3A4 substrateInhibitor0.6784
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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral150 mg
Capsuleoral200 mg
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada24916322009-11-102023-07-04
United States71697912003-07-042023-07-04
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 Reference
  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
  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
  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 Sep 20;118(3):162-164. Pubmed
  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 Aug 22;. Pubmed
  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
External Links
ATC CodesL01XE08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (68.9 KB)
Interactions
Drug Interactions
Drug
AcetohexamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
AfatinibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.
AlogliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Aluminum hydroxideMay decrease the serum concentration of Nilotinib.
AprepitantMay increase the serum concentration of CYP3A4 Substrates.
AtazanavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
AvanafilCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil.
BoceprevirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
BosentanMay decrease the serum concentration of CYP3A4 Substrates.
BosutinibCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.
Brentuximab vedotinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
Calcium carbonateMay decrease the serum concentration of Nilotinib.
CanagliflozinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CarbamazepineCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
ChlorpropamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CilostazolCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol.
CimetidineH2-Antagonists may decrease the serum concentration of Nilotinib.
ClarithromycinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
ClozapineMyelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased.
CodeineCYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine.
ColchicineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine.
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
Dabigatran etexilateP-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DapoxetineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine.
DarunavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
DomperidoneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone.
DronabinolCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.
EnzalutamideCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
EplerenoneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone.
EsomeprazoleProton Pump Inhibitors may decrease the serum concentration of Nilotinib.
EverolimusCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus.
FamotidineH2-Antagonists may decrease the serum concentration of Nilotinib.
FentanylCYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL.
FesoterodineCYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
FosamprenavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
FosaprepitantMay increase the serum concentration of CYP3A4 Substrates.
FosphenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
GliclazideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GlimepirideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GliquidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GlyburideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
HydrocodoneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Hydrocodone.
IfosfamideCYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
ImatinibCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib.
IndinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
Insulin AspartHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin DetemirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin GlargineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin GlulisineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin LisproHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin RegularHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin, isophaneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ItraconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
IvacaftorCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor.
LansoprazoleProton Pump Inhibitors may decrease the serum concentration of Nilotinib.
LedipasvirP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ledipasvir.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
LinagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
LomitapideCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide.
LopinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
LurasidoneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone.
Magnesium oxideMay decrease the serum concentration of Nilotinib.
MetforminHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MetoprololCYP2D6 Inhibitors may increase the serum concentration of Metoprolol.
MifepristoneMay enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
NebivololCYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol.
NefazodoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
NelfinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
NizatidineH2-Antagonists may decrease the serum concentration of Nilotinib.
OmeprazoleProton Pump Inhibitors may decrease the serum concentration of Nilotinib.
OxycodoneCYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased.
PantoprazoleProton Pump Inhibitors may decrease the serum concentration of Nilotinib.
PazopanibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
PhenobarbitalCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
PhenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
PimozideCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide.
PosaconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
PrimidoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
prucaloprideP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
RabeprazoleProton Pump Inhibitors may decrease the serum concentration of Nilotinib.
RanitidineH2-Antagonists may decrease the serum concentration of Nilotinib.
RepaglinideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
RifampicinCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
RifapentineCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
RifaximinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rifaximin.
RitonavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
RivaroxabanP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban.
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
SaquinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
SaxagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
SilodosinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
Sodium bicarbonateAntacids may decrease the serum concentration of Nilotinib.
SuvorexantCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant.
TamoxifenCYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites.
TelaprevirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
TelithromycinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
ThioridazineCYP2D6 Inhibitors may increase the serum concentration of Thioridazine.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TolbutamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
TolvaptanCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan.
TopotecanP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
TrabectedinCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.
TramadolCYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
UlipristalCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal.
VilazodoneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.
VildagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
VoriconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
ZopicloneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone.
Food InteractionsNot Available

Targets

1. Tyrosine-protein kinase ABL1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tyrosine-protein kinase ABL1 P00519 Details

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
  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 Aug 22;. Pubmed
  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
  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
  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. Epub 2009 Oct 12. Pubmed

2. Mast/stem cell growth factor receptor Kit

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Mast/stem cell growth factor receptor Kit P10721 Details

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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2010 Aug 11. Pubmed
  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. Epub 2010 Sep 1. Pubmed
  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. Pubmed
  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. Pubmed

2. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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. Epub 2010 Sep 1. Pubmed
  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. Pubmed

3. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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):169-7http://www.drugbank.ca/lims/molecules/45129. doi: 10.2165/11538700-000000000-00000. Pubmed
  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. Epub 2010 Sep 1. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2010 Sep 1. Pubmed
  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. Pubmed

5. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

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. Epub 2010 Sep 1. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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. Epub 2009 Apr 11. Pubmed
  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. Epub 2009 Sep 28. Pubmed
  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. Epub 2010 Sep 1. Pubmed

2. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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. Epub 2009 Apr 11. Pubmed
  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. Epub 2009 Sep 28. Pubmed
  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. Epub 2010 Sep 1. Pubmed

3. UDP-glucuronosyltransferase 1-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-1 P22309 Details

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. Epub 2010 Sep 1. Pubmed

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Drug created on October 20, 2007 03:39 / Updated on September 16, 2013 17:26