| Drug General Information |
| Drug ID |
D0AZ3C
|
| Drug Name |
Imatinib |
|
| Synonyms |
Cgp 57148; Glamox; Glamox (TN); Gleevec (TN); Glivec (TN); Imatinib (INN); Imatinib (STI571); Imatinib Methansulfonate; Imatinib [INN:BAN]; 112GI019; 152459-95-5; BKJ8M8G5HI; CCRIS 9076; CGP-57148; CHEMBL941; Imatinib free base; STI; UNII-BKJ8M8G5HI |
| 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 |
Gastrointestinal stromal tumor; Leukemia |
| Drug Resistance Mutations |
| Mutation info |
Missense: T315I |
[1] |
| Mutation Frequency |
9 out of 94 patients |
|
| Mutation info |
Missense: F317L |
[1] |
| Mutation Frequency |
9 out of 94 patients |
|
| Mutation info |
Missense: M244V |
[2] |
| Mutation Frequency |
8 out of 53 patients |
|
| Mutation info |
Missense: M351T |
[3] |
| Mutation Frequency |
7 out of 77 patients |
|
| Mutation info |
Missense: E355G |
[4] |
| Mutation Frequency |
7 out of 17 patients |
|
| Mutation info |
Missense: Y253H |
[5] |
| Mutation Frequency |
6 out of 60 patients |
|
| Mutation info |
Missense: G250E |
[6] |
| Mutation Frequency |
6 out of 36 patients |
|
| Mutation info |
Missense: E255K |
[1] |
| Mutation Frequency |
4 out of 94 patients |
|
| Mutation info |
Missense: F359V |
[2] |
| Mutation Frequency |
4 out of 53 patients |
|
| Mutation info |
Missense: V379I |
[7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: S417Y |
[7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: F311L |
[7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: H396R |
[1] |
| Mutation Frequency |
3 out of 94 patients |
|
| Mutation info |
Missense: E255V |
[1] |
| Mutation Frequency |
3 out of 94 patients |
|
| Mutation info |
Missense: Y253F |
[2] |
| Mutation Frequency |
3 out of 53 patients |
|
| Mutation info |
Missense: F486S |
[2] |
| Mutation Frequency |
3 out of 53 patients |
|
| Mutation info |
Missense: L387M |
[8] |
| Mutation Frequency |
3 out of 40 patients |
|
| Mutation info |
Missense: L248V |
[9] |
| Mutation Frequency |
27 out of 144 patients |
|
| Mutation info |
Missense: Q252H |
[10] |
| Mutation Frequency |
23 out of 66 patients in all ABL mutations |
|
| Mutation info |
Missense: E459K |
[1] |
| Mutation Frequency |
2 out of 94 patients |
|
| Mutation info |
Missense: F359C |
[1] |
| Mutation Frequency |
2 out of 94 patients |
|
| Mutation info |
Missense: F311I |
[1] |
| Mutation Frequency |
2 out of 94 patients |
|
| Mutation info |
Missense: E459G |
[1] |
| Mutation Frequency |
2 out of 94 patients |
|
| Mutation info |
Missense: F359I |
[2] |
| Mutation Frequency |
2 out of 53 patients |
|
| Mutation info |
Missense: L298V |
[6] |
| Mutation Frequency |
2 out of 36 patients |
|
| Mutation info |
Missense: D276G |
[11] |
| Mutation Frequency |
16 out of 49 patients in all ABL mutations |
|
| Mutation info |
Missense: L364I |
[1] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: A397P |
[3] |
| Mutation Frequency |
1 out of 77 patients |
|
| Mutation info |
Missense: E450G |
[12] |
| Mutation Frequency |
1 out of 62 patients |
|
| Mutation info |
Missense: H396P |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: L384M |
[13] |
| Mutation Frequency |
1 out of 4 patients |
|
| Mutation info |
Missense: V299L |
[14], [15], [16], [17] |
|
| Mutation info |
Missense: M388L |
[1], [2], [14] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: F382L |
[18], [2], [14] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: E450A |
[12], [19], [14] |
| Mutation Frequency |
1 out of 62 patients |
|
| Mutation info |
Missense: I418V |
[2], [19], [14] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: A433T |
[1], [20], [14] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: E292V |
[1], [2], [14] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: E355A |
[1], [14], [21] |
| Mutation Frequency |
2 out of 94 patients |
|
| Mutation info |
Missense: E453K |
[1], [2], [14] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: F317V |
[8], [14], [17] |
| Mutation Frequency |
1 out of 40 patients |
|
| Mutation info |
Missense: L273M |
[2], [22], [14] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: T277A |
[14], [15], [7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: V289F |
[6], [23], [21] |
| Mutation Frequency |
1 out of 40 patients |
|
| Mutation info |
Missense: S438C |
[14], [15], [24] |
|
| Mutation info |
Missense: M343T |
[18], [14] |
|
| Mutation info |
Missense: Q252R |
[18], [14] |
|
| Mutation info |
Missense: E450K |
[25], [14] |
| Mutation Frequency |
1 out of 55 patients |
|
| Mutation info |
Missense: F317C |
[14], [17] |
|
| Mutation info |
Missense: F317I |
[14], [17] |
|
| Mutation info |
Missense: L324Q |
[14], [26] |
|
| Mutation info |
Missense: P480L |
[25], [14] |
| Mutation Frequency |
1 out of 55 patients |
|
| Mutation info |
Missense: E279K |
[14], [27] |
|
| Mutation info |
Missense: Y320C |
[14], [15] |
|
| Mutation info |
Missense: E453A |
[14], [24] |
|
| Mutation info |
Missense: L387F |
[14], [24] |
|
| Mutation info |
Missense: E275K |
[14], [28] |
|
| Mutation info |
Missense: E453G |
[14], [28] |
|
| Mutation info |
Missense: V289A |
[14] |
|
| Mutation info |
Missense: A399T |
[15] |
|
| Mutation info |
Missense: F359A |
[11] |
| Mutation Frequency |
16 out of 49 patients in all ABL mutations |
|
| Mutation info |
Missense: T315N |
[11] |
| Mutation Frequency |
16 out of 49 patients in all ABL mutations |
|
| Mutation info |
Missense: Q252E |
[29] |
| Mutation Frequency |
30% of the patients |
|
| Mutation info |
Missense: E459Q |
[1] |
| Mutation Frequency |
1 out of 94 patients |
|
| Mutation info |
Missense: D482V |
[2] |
| Mutation Frequency |
4 out of 53 patients |
|
| Mutation info |
Missense: E279Z |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: E282G |
[2] |
| Mutation Frequency |
2 out of 53 patients |
|
| Mutation info |
Missense: E352D |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: E352G |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: E453D |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: G251D |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: R328M |
[2] |
| Mutation Frequency |
1 out of 53 patients |
|
| Mutation info |
Missense: N374Y |
[30] |
|
| Mutation info |
Missense: E279Y |
[19] |
|
| Mutation info |
Missense: E355? |
[19] |
|
| Mutation info |
Missense: E450? |
[19] |
|
| Mutation info |
Missense: E453L |
[19] |
|
| Mutation info |
Missense: F359* |
[19] |
|
| Mutation info |
Missense: F359? |
[19] |
|
| Mutation info |
Missense: Q252K |
[20] |
| Mutation Frequency |
1 out of 21 patients |
|
| Mutation info |
Missense: K294 > RGG |
[31] |
|
| Mutation info |
Missense: A344V |
[14] |
|
| Mutation info |
Missense: A350V |
[14] |
|
| Mutation info |
Missense: A365V |
[14] |
|
| Mutation info |
Missense: A366G |
[14] |
|
| Mutation info |
Missense: A380T |
[14] |
|
| Mutation info |
Missense: D363Y |
[14] |
|
| Mutation info |
Missense: E258D |
[14] |
|
| Mutation info |
Missense: E275Q |
[14] |
|
| Mutation info |
Missense: E292Q |
[14] |
|
| Mutation info |
Missense: E355D |
[14] |
|
| Mutation info |
Missense: E373K |
[14] |
|
| Mutation info |
Missense: E450V |
[14] |
|
| Mutation info |
Missense: E453V |
[14] |
|
| Mutation info |
Missense: E459A |
[14] |
|
| Mutation info |
Missense: E459V |
[14] |
|
| Mutation info |
Missense: E507G |
[14] |
|
| Mutation info |
Missense: F359L |
[14] |
|
| Mutation info |
Missense: G250R |
[14] |
|
| Mutation info |
Missense: H396A |
[14] |
|
| Mutation info |
Missense: I242T |
[14] |
|
| Mutation info |
Missense: I293V |
[14] |
|
| Mutation info |
Missense: I418S |
[14] |
|
| Mutation info |
Missense: K247R |
[14] |
|
| Mutation info |
Missense: L370P |
[14] |
|
| Mutation info |
Missense: L387V |
[14] |
|
| Mutation info |
Missense: M237V |
[14] |
|
| Mutation info |
Missense: M472I |
[14] |
|
| Mutation info |
Missense: S417F |
[14] |
|
| Mutation info |
Missense: V280A |
[14] |
|
| Mutation info |
Missense: V289I |
[14] |
|
| Mutation info |
Missense: V371A |
[14] |
|
| Mutation info |
Missense: W261L |
[14] |
|
| Mutation info |
Missense: Y342H |
[14] |
|
| Mutation info |
Missense: Y393C |
[14] |
|
| Mutation info |
Missense: Y353H |
[6] |
| Mutation Frequency |
4 out of 36 patients |
|
| Mutation info |
Missense: K419E |
[27] |
|
| Mutation info |
Missense: E494G |
[15] |
|
| Mutation info |
Missense: K378R |
[15] |
|
| Mutation info |
Missense: M351K |
[15] |
|
| Mutation info |
Missense: V256L |
[15] |
|
| Mutation info |
Missense: T315A |
[17] |
|
| Mutation info |
Missense: D276A |
[7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: L340L |
[7] |
| Mutation Frequency |
38 out of 45 patients |
|
| Mutation info |
Missense: D276N |
[24] |
|
| Mutation info |
Missense: E279A |
[24] |
|
| Mutation info |
Missense: G251E |
[21] |
| Mutation Frequency |
1 out of 125 patients |
|
| Mutation info |
Missense: N368S |
[21] |
| Mutation Frequency |
1 out of 125 patients |
|
| Mutation info |
Missense: G398R |
[32] |
| Mutation Frequency |
33% of the patients |
|
| Target Name |
Mast/stem cell growth factor receptor Kit (KIT) |
Target Info |
| Gene Name |
KIT |
| Uniprot ID |
KIT_HUMAN |
| Species |
Homo sapiens |
| Reference Sequence |
MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD
PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV
DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH
RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS
SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN
VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE
DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR
LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS
SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV
MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF
GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC
TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE
YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM
AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES
IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY
DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV
GSTASSSQPLLVHDDV [Homo sapiens]
|
| Targeted Disease |
Gastrointestinal stromal tumor; Leukemia |
| Drug Resistance Mutations |
| Mutation info |
Missense: V654A |
[33] |
| Mutation Frequency |
9 out of 33 patients |
|
| Mutation info |
Missense: Y823D |
[34] |
| Mutation Frequency |
9 out of 32 patients |
|
| Mutation info |
Missense: N822K |
[36] |
| Mutation Frequency |
8 out of 10 patients in all KIT mutations |
|
| Mutation info |
Missense: D816H |
[36] |
| Mutation Frequency |
8 out of 10 patients in all KIT mutations |
|
| Mutation info |
Missense: C809G |
[36] |
| Mutation Frequency |
8 out of 10 patients in all KIT mutations |
|
| Mutation info |
Missense: T670I |
[37] |
| Mutation Frequency |
3 out of 78 patients |
|
| Mutation info |
Missense: D820Y |
[33] |
| Mutation Frequency |
3 out of 33 patients |
|
| Mutation info |
Missense: D820E |
[33] |
| Mutation Frequency |
3 out of 33 patients |
|
| Mutation info |
Missense: D820G |
[38] |
| Mutation Frequency |
21 out of 33 patients in all KIT mutations |
|
| Mutation info |
Missense: A829P |
[37] |
| Mutation Frequency |
2 out of 78 patients |
|
| Mutation info |
Missense: H697Y |
[39], [40], [41] |
|
| Mutation info |
Missense: V559I |
[39], [40], [41] |
|
| Mutation info |
Missense: N822Y |
[38], [42], [33] |
| Mutation Frequency |
3 out of 33 patients |
|
| Mutation info |
Missense: T670E |
[43], [33] |
| Mutation Frequency |
14 out of 32 patients in all KIT mutations |
|
| Mutation info |
Missense: D820A |
[38], [37] |
| Mutation Frequency |
21 out of 33 patients in all KIT mutations |
|
| Mutation info |
Missense: D816E |
[43], [44] |
| Mutation Frequency |
14 out of 32 patients in all KIT mutations |
|
| Mutation info |
Missense: K642E |
[34], [33] |
| Mutation Frequency |
1 out of 33 patients |
|
| Mutation info |
Missense: D816G |
[46] |
|
| Mutation info |
Missense: D716N |
[46] |
|
| Mutation info |
Missense: S709F |
[43] |
|
| Mutation info |
Missense: D816A |
[37] |
| Mutation Frequency |
1 out of 78 patients |
|
| Mutation info |
Missense: S821F |
[47] |
| Mutation Frequency |
1 out of 3 patients |
|
| Mutation info |
Deletion: D579 |
[33] |
| Mutation Frequency |
1 out of 33 patients |
|
| Mutation info |
Missense: N680K |
[33] |
| Mutation Frequency |
1 out of 33 patients |
|
| Mutation info |
Missense: Y578C |
[33] |
| Mutation Frequency |
2 out of 33 patients |
|
| Target Name |
Platelet-derived growth factor receptor alpha (PDGFRA) |
Target Info |
| Gene Name |
PDGFRA |
| Uniprot ID |
PGFRA_HUMAN |
| Species |
Homo sapiens |
| Reference Sequence |
MGTSHPAFLVLGCLLTGLSLILCQLSLPSILPNENEKVVQLNSSFSLRCFGESEVSWQYP
MSEEESSDVEIRNEENNSGLFVTVLEVSSASAAHTGLYTCYYNHTQTEENELEGRHIYIY
VPDPDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYDSRQGFNG
TFTVGPYICEATVKGKKFQTIPFNVYALKATSELDLEMEALKTVYKSGETIVVTCAVFNN
EVVDLQWTYPGEVKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVK
EMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEVRAYPPPRISWLKNNLTLIENL
TEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDL
VDDHHGSTGGQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRD
RSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAPTLRSELTVAAAVLVLLVIVII
SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLG
SGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNL
LGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSY
VILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKN
LLSDDNSEGLTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLA
RDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMM
VDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKK
SYEKIHLDFLKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYII
PLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTFIKREDETIEDIDMMDDIGIDS
SDLVEDSFL [Homo sapiens]
|
| Targeted Disease |
Gastrointestinal stromal tumor; Leukemia |
| Drug Resistance Mutations |
| Mutation info |
Missense: D842V |
[35] |
| Mutation Frequency |
9 out of 18 patients |
|
| Target Name |
Serine/threonine-protein kinase (B-raf) |
Target Info |
| Gene Name |
BRAF |
| Uniprot ID |
BRAF_HUMAN |
| Species |
Homo sapiens |
| Reference Sequence |
MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEH
IEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTV
TSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDS
LKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRK
TFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPI
PQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQR
DRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSP
GPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDV
AVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHH
LHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV
KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNIN
NRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS
LPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH [Homo sapiens
]
|
| Targeted Disease |
Gastrointestinal stromal tumor; Leukemia |
| Drug Resistance Mutations |
| Mutation info |
Missense: V600E |
[45] |
|
| References |
| REF 1 |
Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations. Blood. 2009 Sep 3;114(10):2037-43.
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| REF 2 |
Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib. Blood. 2009 Sep 24;114(13):2598-605.
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| REF 3 |
BCR-ABL isoforms associated with intrinsic or acquired resistance to imatinib: more heterogeneous than just ABL kinase domain point mutations Med Oncol. 2012 Mar;29(1):219-26.
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| REF 4 |
Characterization of the rpsL and rrs genes of streptomycin-resistant clinical isolates of Mycobacterium tuberculosis in Japan. J Appl Microbiol. 1997 Nov;83(5):634-40.
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| REF 5 |
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.
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| REF 6 |
Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: do BCR-ABL kinase domain mutations affect patient survival First multicenter Argentinean study. Leuk Lymphoma. 2011 Sep;52(9):1720-6.
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| REF 7 |
Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors. Med Clin (Barc). 2013 Aug 4;141(3):95-9.
|
| REF 8 |
Mutations in ABL kinase domain are associated with inferior progression-free survival. Leuk Lymphoma. 2010 Jun;51(6):1072-8.
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| REF 9 |
Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in ... Blood. 2003 Jul 1;102(1):276-83.
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| REF 10 |
Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002 Nov;16(11):2190-6.
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| REF 11 |
High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J. 2004;5(1):55-60.
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| REF 12 |
Rapid and sensitive allele-specific (AS)-RT-PCR assay for detection of T315I mutation in chronic myeloid leukemia patients treated with tyrosine-kinase inhibitors. Clin Exp Med. 2011 Mar;11(1):55-9.
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| REF 13 |
The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109.
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| REF 14 |
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.
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| REF 15 |
Impact of BCR-ABL mutations on response to dasatinib after imatinib failure in elderly patients with chronic-phase chronic myeloid leukemia. Ann Hematol. 2013 Jan;92(2):179-83.
|
| REF 16 |
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.
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| REF 17 |
BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships. Blood. 2013 Jan 17;121(3):489-98.
|
| REF 18 |
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell. 2002 Aug;2(2):117-25.
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| REF 19 |
Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients. Ann Hematol. 2011 Jan;90(1):47-52.
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| REF 20 |
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.
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| REF 21 |
BCR-ABL kinase domain mutations, including 2 novel mutations in imatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical outcome. Leuk Res. 2014 Apr;38(4):454-9.
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| REF 22 |
Spectrum of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia from India with suspected resistance to imatinib-mutations are rare and have different distributions. Leuk Lymphoma. 2009 Dec;50(12):2092-5.
|
| REF 23 |
Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients. Hematol Rep. 2012 Nov 19;4(4):e23.
|
| REF 24 |
Detection of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on imatinib. Hematology. 2013 Nov;18(6):328-33.
|
| REF 25 |
Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors. Hematol Oncol. 2010 Jun;28(2):82-8.
|
| REF 26 |
Increased genomic instability may contribute to the development of kinase domain mutations in chronic myeloid leukemia. Int J Hematol. 2014 Dec;100(6):567-74.
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| REF 27 |
Role of treatment in the appearance and selection of BCR-ABL1 kinase domain mutations. Mol Diagn Ther. 2012 Aug 1;16(4):251-9.
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| REF 28 |
BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance. Br J Cancer. 2013 Sep 17;109(6):1593-8.
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| REF 29 |
Evidence of ABL-kinase domain mutations in highly purified primitive stem cell populations of patients with chronic myelogenous leukemia. Biochem Biophys Res Commun. 2004 Oct 22;323(3):728-30.
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| REF 30 |
Kinase domain mutations and responses to dose escalation in chronic myeloid leukemia resistant to standard dose imatinib mesylate. Leuk Lymphoma. 2010 Jan;51(1):79-84.
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| REF 31 |
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 32 |
Incidence and clinical importance of BCR-ABL1 mutations in Iranian patients with chronic myeloid leukemia on imatinib. J Hum Genet. 2015 May;60(5):253-8.
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| REF 33 |
Massively parallel sequencing fails to detect minor resistant subclones in tissue samples prior to tyrosine kinase inhibitor therapy. BMC Cancer. 2015 Apr 15;15:291.
|
| REF 34 |
Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors. J Cancer Res Clin Oncol. 2010 Jul;136(7):1065-71.
|
| REF 35 |
Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors. Cancer Res Treat. 2016 Apr;48(2):546-52.
|
| REF 36 |
Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5398-405.
|
| REF 37 |
Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008 Nov 20;26(33):5352-9.
|
| REF 38 |
Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006 Oct 10;24(29):4764-74.
|
| REF 39 |
Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation. Lab Invest. 2007 Apr;87(4):365-71.
|
| REF 40 |
Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp Hematol. 2011 Aug;39(8):859-65.e2.
|
| REF 41 |
Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells. Pigment Cell Melanoma Res. 2013 Jul;26(4):518-26.
|
| REF 42 |
Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008 Sep;216(1):64-74.
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| REF 43 |
Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006 Mar 15;12(6):1743-9.
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| REF 44 |
Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol. 2008 Jul 1;98(1):27-33.
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| REF 45 |
KIT and BRAF heterogeneous mutations in gastrointestinal stromal tumors after secondary imatinib resistance. Gastric Cancer. 2015 Oct;18(4):796-802.
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| REF 46 |
Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005 Feb;128(2):270-9.
|
| REF 47 |
Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor. Target Oncol. 2015 Dec;10(4):597-601.
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