Drug General Information
Drug ID	D00STL
Drug Name	Nilotinib
Synonyms	NIL; Nilotinibum; Tasigna (Novartis); Nilotinib (INN/USAN); Nilotinib, AMN107, Tasigna; Tasigna, AMN-107, Nilotinib; L-1-yl)-3-(trifluoromethyl)phenyl]benzamide; Benzamide, 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-(9CI); 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazo; 4-Methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 4-Methyl-N-[3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl]-3-[[4-(pyridin-3-yl)pyrimidin-2-yl]amino]benzamide; 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide; Nilotinib (BCR-ABL inhibitor 2nd gen)
Drug Type	Small molecular drug
Therapeutic Class	Anticancer Agents
Company	Novartis AG
Structure
Drug Resistance Mutations
Target Name	Tyrosine-protein kinase ABL1(ABL1)				Target Info
Gene Name	ABL1
Uniprot ID	ABL1_HUMAN
Species	Homo sapiens
Reference Sequence	MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSE NDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVN SLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTAS DGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERT DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFI HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKS DVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP SDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAE HRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLF SALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSP KPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSAS CVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTV TPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGS ALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPP PPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVL PATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPE RIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNK FAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR [Homo sap iens]
Targeted Disease	Leukemia
Drug Resistance Mutations	Mutation info Missense: Y253H [1], [2]
	Mutation info Missense: E255V [1], [3] Mutation Frequency 1 out of 21 patients
	Mutation info Missense: E255K [1], [3] Mutation Frequency 2 out of 21 patients
	Mutation info Missense: F359C [1], [3] Mutation Frequency 2 out of 21 patients
	Mutation info Missense: T315I [5]
	Mutation info Missense: M351T [6]
	Mutation info Missense: H396R [2]
	Mutation info Missense: G250E [7]
	Mutation info Missense: F359V [1]
	Mutation info Missense: F359I [1]
	Mutation info Missense: T315V [8]
Target Name	UDP-glucuronosyltransferase 1-1 (UGT1A1)				Target Info
Gene Name	UGT1A1
Uniprot ID	UD11_HUMAN
Species	Homo sapiens
Reference Sequence	MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH [Homo sapiens]
Targeted Disease	Leukemia
Drug Resistance Mutations	Mutation info Missense: P229Q [4]
	Mutation info Missense: G71R [4]
References
REF 1	BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011 Aug 4;118(5):1208-15.
REF 2	Role of treatment in the appearance and selection of BCR-ABL1 kinase domain mutations. Mol Diagn Ther. 2012 Aug 1;16(4):251-9.
REF 3	Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. Blood. 2011 Mar 31;117(13):3641-7.
REF 4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 5	Analysis of mutations in the BCR-ABL1 kinase domain, using direct sequencing: detection of the T315I mutation in bone marrow CD34+ cells of a patient with chronic myelogenous leukemia 6 months prior to its emergence in peripheral blood. Mol Diagn Ther. 2012 Jun 1;16(3):163-6.
REF 6	Sequential development of mutant clones in an imatinib resistant chronic myeloid leukaemia patient following sequential treatment with multiple tyrosine kinase inhibitors: an emerging problem Cancer Chemother Pharmacol. 2009 Jun;64(1):195-7.
REF 7	Outcome of patients with chronic myeloid leukemia with multiple ABL1 kinase domain mutations receiving tyrosine kinase inhibitor therapy. Haematologica. 2011 Jun;96(6):918-21.
REF 8	Three novel patient-derived BCR/ABL mutants show different sensitivity to second and third generation tyrosine kinase inhibitors. Am J Hematol. 2012 Nov;87(11):E125-8.

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