Drug General Information
Drug ID D0E6XR
Drug Name Dasatinib
Synonyms Sprycel (TN); BMS 354825; BMS-354825; BMS-354825, Sprycel, BMS354825, Dasatinib; BMS354825; Dasatinib (USAN); Dasatinib [USAN]; Dasatinib anhydrous; Dasatinib, BMS 354825; Dasatinibum; Sprycel; Spyrcel
Drug Type Small molecular drug
Therapeutic Class Anticancer Agents
Company Bristol Myers Squibb
Structure D0E6XR
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: F317L [1]
Mutation Frequency 4 out of 60 patients
Mutation info Missense: T315I [2]
Mutation Frequency 12 out of 17 patients
Mutation info Missense: V299L [3], [4], [5], [6], [7]
Mutation info Missense: Y253H [4], [8], [9]
Mutation info Missense: G250E [3], [4], [8]
Mutation info Missense: E255K [4], [10], [2]
Mutation Frequency 1 out of 21 patients
Mutation info Missense: E355G [3], [4]
Mutation info Missense: T315A [5], [11]
Mutation info Missense: F359V [7]
Mutation info Missense: F359I [3]
Mutation info Missense: T495R [3]
Mutation info Missense: D444Y [4]
Mutation info Missense: L273M [4]
Mutation info Missense: V379I [4]
Mutation info Missense: Y253F [4]
Mutation info Missense: Y353H [4]
Mutation info Missense: F317C [5]
Mutation info Missense: F317I [5]
Mutation info Missense: F317V [5]
Mutation info Missense: F317R [11]
References
REF 1 BCR-ABL1 mutations in patients with imatinib-resistant Philadelphia chromosome-positive leukemia by use of the PCR-Invader assay. Leuk Res. 2011 May;35(5):598-603.
REF 2 Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011 Dec 15;118(25):6521-8.
REF 3 Complexity of BCR-ABL kinase domain mutations during the course of therapy with tyrosine kinase inhibitors in chronic myeloid leukemia. Am J Hematol. 2009 Apr;84(4):256-7.
REF 4 Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant chronic myelogenous leukemia patients. Leuk Res. 2011 Jan;35(1):38-43.
REF 5 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 6 Characteristics and outcomes of patients with V299L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood. 2012 Oct 18;120(16):3382-3.
REF 7 Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64.
REF 8 A novel insertion mutation of K294RGG within BCR-ABL kinase domain confers imatinib resistance: sequential analysis of the clonal evolution in a patient with chronic myeloid leukemia in blast crisis. Int J Hematol. 2011 Feb;93(2):237-42.
REF 9 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 10 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 11 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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