| 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 |
|
| 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.
|
