Drug General Information |
Drug ID |
D0E6XR |
Drug Name |
Dasatinib |
Drug Info
|
Synonyms |
Dasatinibum; Sprycel; Spyrcel; Dasatinib [USAN]; Dasatinib anhydrous; BMS 354825; BMS354825; BMS-354825; Dasatinib (USAN); Dasatinib, BMS 354825; SPRYCEL (TN); Sprycel (TN); BMS-354825, Sprycel, BMS354825, Dasatinib; N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate; N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide; N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide; N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE; (18F)-N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide; 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide |
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: T315I |
[555817]
|
Mutation Prevalence |
12 out of 17 patients |
|
Mutation info |
Missense: E255K |
[555765],
[555785],
[555817]
|
Mutation Prevalence |
1 out of 21 patients |
|
Mutation info |
Missense: F317L |
[555789]
|
Mutation Prevalence |
4 out of 60 patients |
|
|
|
|
Mutation info |
Missense: F359V |
[556073]
|
|
Mutation info |
Missense: D444Y |
[555765]
|
|
Mutation info |
Missense: L273M |
[555765]
|
|
Mutation info |
Missense: V379I |
[555765]
|
|
Mutation info |
Missense: Y253F |
[555765]
|
|
Mutation info |
Missense: Y353H |
[555765]
|
|
Mutation info |
Missense: F317C |
[555806]
|
|
Mutation info |
Missense: F317I |
[555806]
|
|
Mutation info |
Missense: F317V |
[555806]
|
|
Mutation info |
Missense: F317R |
[555892]
|
|
|
Mutation info |
Missense: F359I |
[555699]
|
|
Mutation info |
Missense: T495R |
[555699]
|
|
|
References |
Ref 528715 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. |
Ref 536577 | Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther. 2007 Nov;29(11):2289-308. |
Ref 541021 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5678). |
Ref 551871 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 |
Ref 555699 | 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. doi: 10.1002/ajh.21366. |
Ref 555765 | Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant chronic myelogenous leukemia patients. Leuk Res. 2011 Jan;35(1):38-43. doi: 10.1016/j.leukres.2010.06.030. Epub 2010 Jul 29. |
Ref 555785 | 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. doi: 10.1182/blood-2010-08-302679. Epub 2010 Dec 14. |
Ref 555789 | 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. doi: 10.1016/j.leukres.2010.12.006. Epub 2011 Jan 15. |
Ref 555791 | 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. doi: 10.1007/s12185-011-0766-2. Epub 2011 Jan 25. |
Ref 555796 | 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. doi: 10.3324/haematol.2010.039321. Epub 2011 Feb 28. |
Ref 555806 | 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. doi: 10.1182/blood-2010-12-326405. Epub 2011 May 11. |
Ref 555817 | Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011 Dec 15;118(25):6521-8. doi: 10.1182/blood-2011-05-351403. Epub 2011 Sep 19. |
Ref 555892 | 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. doi: 10.1002/ajh.23338. Epub 2012 Oct 9. |
Ref 555898 | 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. doi: 10.1182/blood-2012-04-424192. |
Ref 556073 | 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. doi: 10.1002/cncr.29646. Epub 2015 Aug 26. |