Chemical: Drug
nilotinib

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


Annotated Labels

  1. FDA Label for nilotinib and ABL1,BCR
  2. FDA Label for nilotinib and UGT1A1
  3. EMA Label for nilotinib and ABL1,BCR
  4. HCSC Label for nilotinib and ABI1,BCR
  5. HCSC Label for nilotinib and UGT1A1






PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for nilotinib

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA UGT1A1 *1 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *6 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *27 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *28 N/A N/A N/A
No VIP available CA VA
rs1061018 NC_000004.11:g.89042853A>G, NC_000004.12:g.88121701A>G, NG_032067.2:g.114622T>C, NM_001257386.1:c.623T>C, NM_004827.2:c.623T>C, NP_001244315.1:p.Phe208Ser, NP_004818.2:p.Phe208Ser, XM_005263354.1:c.623T>C, XM_005263354.2:c.623T>C, XM_005263355.1:c.623T>C, XM_005263355.2:c.623T>C, XM_005263356.1:c.623T>C, XM_005263356.2:c.623T>C, XM_011532420.1:c.623T>C, XP_005263411.1:p.Phe208Ser, XP_005263412.1:p.Phe208Ser, XP_005263413.1:p.Phe208Ser, XP_011530722.1:p.Phe208Ser, rs386514545
A > G
SNP
F208S
No VIP available No Clinical Annotations available VA
rs121913459 NC_000009.11:g.133748283C>T, NC_000009.12:g.130872896C>T, NG_012034.1:g.164016C>T, NM_005157.5:c.944C>T, NM_007313.2:c.1001C>T, NP_005148.2:p.Thr315Ile, NP_009297.2:p.Thr334Ile, XM_005272177.1:c.998C>T, XP_005272234.1:p.Thr333Ile
C > T
SNP
T315I
No VIP available CA VA
rs2231137 NC_000004.11:g.89061114C>T, NC_000004.12:g.88139962C>T, NG_032067.2:g.96361G>A, NM_001257386.1:c.34G>A, NM_004827.2:c.34G>A, NP_001244315.1:p.Val12Met, NP_004818.2:p.Val12Met, XM_005263354.1:c.34G>A, XM_005263354.2:c.34G>A, XM_005263355.1:c.34G>A, XM_005263355.2:c.34G>A, XM_005263356.1:c.34G>A, XM_005263356.2:c.34G>A, XM_011532420.1:c.34G>A, XP_005263411.1:p.Val12Met, XP_005263412.1:p.Val12Met, XP_005263413.1:p.Val12Met, XP_011530722.1:p.Val12Met
C > T
SNP
V12M
No VIP available No Clinical Annotations available VA
rs2231142 NC_000004.11:g.89052323G>T, NC_000004.12:g.88131171G>T, NG_032067.2:g.105152C>A, NM_001257386.1:c.421C>A, NM_004827.2:c.421C>A, NP_001244315.1:p.Gln141Lys, NP_004818.2:p.Gln141Lys, XM_005263354.1:c.421C>A, XM_005263354.2:c.421C>A, XM_005263355.1:c.421C>A, XM_005263355.2:c.421C>A, XM_005263356.1:c.421C>A, XM_005263356.2:c.421C>A, XM_011532420.1:c.421C>A, XP_005263411.1:p.Gln141Lys, XP_005263412.1:p.Gln141Lys, XP_005263413.1:p.Gln141Lys, XP_011530722.1:p.Gln141Lys, rs12721641, rs28365035, rs3736117, rs52809243, rs58973676
G > T
SNP
Q141K
No VIP available CA VA
rs41282401 NC_000004.11:g.89036166C>G, NC_000004.12:g.88115014C>G, NG_032067.2:g.121309G>C, NM_001257386.1:c.886G>C, NM_004827.2:c.886G>C, NP_001244315.1:p.Asp296His, NP_004818.2:p.Asp296His, XM_005263354.1:c.886G>C, XM_005263354.2:c.886G>C, XM_005263355.1:c.886G>C, XM_005263355.2:c.886G>C, XM_005263356.1:c.886G>C, XM_005263356.2:c.886G>C, XM_011532420.1:c.886G>C, XP_005263411.1:p.Asp296His, XP_005263412.1:p.Asp296His, XP_005263413.1:p.Asp296His, XP_011530722.1:p.Asp296His
C > G
SNP
D296H
No VIP available No Clinical Annotations available VA
rs58818712 NC_000004.11:g.89018678A>C, NC_000004.12:g.88097526A>C, NG_032067.2:g.138797T>G, NM_001257386.1:c.1574T>G, NM_004827.2:c.1574T>G, NP_001244315.1:p.Leu525Arg, NP_004818.2:p.Leu525Arg, XM_005263354.1:c.1574T>G, XM_005263354.2:c.1574T>G, XM_005263355.1:c.1574T>G, XM_005263355.2:c.1574T>G, XM_005263356.1:c.1568T>G, XM_005263356.2:c.1568T>G, XM_011532420.1:c.1574T>G, XP_005263411.1:p.Leu525Arg, XP_005263412.1:p.Leu525Arg, XP_005263413.1:p.Leu523Arg, XP_011530722.1:p.Leu525Arg, rs61735384
A > C
SNP
L525R
No VIP available CA VA
rs8175347
(TA)6 > (TA)5
(TA)6 > (TA)7
(TA)6 > (TA)8
microsatellite
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • amn-107
  • amn107
Trade Names
  • Tasigna
  • Tasigna (Novartis)
Brand Mixture Names

PharmGKB Accession Id

PA165958345

Type(s):

Drug

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 R ), another tyrosine kinase inhibitor currently used as a first-line treatment.

Source: Drug Bank

Pharmacogenetics

Nilotinib is targeted against the BCR-ABL1 fusion protein characteristic of chronic myeloid leukemia. It is not effective against the imatinib resistant variant of BCR-ABL1, T315I (rs121913459) [Article:23065514].

Source: PharmGKB [Article:23065514]

Indication

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

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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).

Source: Drug Bank

Pharmacology

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).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Absorption

Orally available

Source: Drug Bank

Half-Life

15 hours

Source: Drug Bank

Chemical Properties

Chemical Formula

C28H22F3N7O

Source: Drug Bank

Isomeric SMILES

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

Source: Drug Bank

Canonical 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

Source: Drug Bank

Average Molecular Weight

529.5158

Source: Drug Bank

Monoisotopic Molecular Weight

529.183792976

Source: Drug Bank

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

Source: Drug Bank

InChI String

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)

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ABL1 [PMID:22616642] (source: PharmGKB )

Drug Interactions

Interaction Description
tamoxifen - nilotinib Nilotinib may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamoxifen - nilotinib Nilotinib may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamsulosin - nilotinib Nilotinib, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nilotinib is initiated, discontinued, or dose changed. (source: Drug Bank )
tamsulosin - nilotinib Nilotinib, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nilotinib is initiated, discontinued, or dose changed. (source: Drug Bank )
telithromycin - nilotinib Telithromycin may reduce clearance of Nilotinib. Concomitant therapy should be avoided. (source: Drug Bank )
thiothixene - nilotinib May cause additive QTc-prolonging effects. Concomitant therapy should be avoided. (source: Drug Bank )
thiothixene - nilotinib May cause additive QTc-prolonging effects. Concomitant therapy should be avoided. (source: Drug Bank )
topotecan - nilotinib The p-glycoprotein inhibitor, Nilotinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided. (source: Drug Bank )
toremifene - nilotinib May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated. (source: Drug Bank )
tramadol - nilotinib Nilotinib may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
trastuzumab - nilotinib Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank )
trimipramine - nilotinib May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated. (source: Drug Bank )
voriconazole - nilotinib Voriconazole may increase the serum concentration of nilotinib by inhibiting its metabolism by CYP3A4. Additive QTc prolongation may also occur. Concomitant therapy should be avoided. (source: Drug Bank )
vorinostat - nilotinib Additive QTc prolongation may occur. Concomitant therapy should be avoided. (source: Drug Bank )
ziprasidone - nilotinib Additive QTc-prolongation may occur. Concomitant therapy should be avoided. (source: Drug Bank )
zuclopenthixol - nilotinib Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided. (source: Drug Bank )

Curated Information ?

Publications related to nilotinib: 22

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic agreement between two cancer cell line data sets. Nature. 2015. Cancer Cell Line Encyclopedia Consortium, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Eradication of T315I mutation in chronic myeloid leukemia without third-generation tyrosine kinase inhibitor: a case report. Pharmacogenomics. 2015. Venton Geoffroy, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer cell. 2014. Zabriskie Matthew S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug metabolism and disposition: the biological fate of chemicals. 2014. Filppula Anne M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction of the Efflux Transporters ABCB1 and ABCG2 With Imatinib, Nilotinib, and Dasatinib. Clinical pharmacology and therapeutics. 2014. Eadie L N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Single-nucleotide polymorphisms of ABCG2 increase the efficacy of tyrosine kinase inhibitors in the K562 chronic myeloid leukemia cell line. Pharmacogenetics and genomics. 2014. Skoglund Karin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug metabolism and drug interactions. 2014. Khurana Varun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Influence of UGT1A1 6, 27, and 28 polymorphisms on nilotinib-induced hyperbilirubinemia in Japanese patients with chronic myeloid leukemia. Drug metabolism and pharmacokinetics. 2014. Abumiya Maiko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inconsistency in large pharmacogenomic studies. Nature. 2013. Haibe-Kains Benjamin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. American journal of hematology. 2013. Cortes J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia. Haematologica. 2013. Lange Thoralf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia. International journal of clinical oncology. 2013. Shibata Takashi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Playing Russian Roulette With Tyrosine Kinase Inhibitors. Clinical pharmacology and therapeutics. 2012. Szmulewitz R Z, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Off-target effects of BCR-ABL1 inhibitors and their potential long-term implications in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2012. Steegmann Juan Luis, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia. Expert review of anticancer therapy. 2012. Keller-V Amsberg Gunhild, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on pyrimidines, pyridines and pyrroles. Clinical pharmacokinetics. 2011. Di Gion Paola, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2). BMC structural biology. 2009. Winger Jonathan A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clinical therapeutics. 2008. Deremer David L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2007. Singer J B, et al. PubMed

LinkOuts

DrugBank:
DB04868
ChEBI:
52172
PubChem Compound:
644241
PubChem Substance:
99443226
ChemSpider:
559260

Clinical Trials

These are trials that mention nilotinib and are related to either pharmacogenetics or pharmacogenomics.

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NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.