                         SEQUENCE LISTING

<110>  Deciphera Pharmaceuticals, LLC
 
<120>  Use of 
       1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-napht
       hyridin-3-yl]-2-fluorophenyl]-3-phenylurea and analogs for the 
       treatment of cancers associated with genetic abnormalities in 
       platelet derived growth factor receptor alpha

<130>  DECP-073/00US 313114-2516

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  792
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Glu His His His His His His His His Met Ala Pro Ile Leu Gly 
1               5                   10                  15      


Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro Thr Arg Leu Leu Leu Glu 
            20                  25                  30          


Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu Tyr Glu Arg Asp Glu Gly 
        35                  40                  45              


Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu Gly Leu Glu Phe Pro Asn 
    50                  55                  60                  


Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys Leu Thr Gln Ser Met Ala 
65                  70                  75                  80  


Ile Ile Arg Tyr Ile Ala Asp Lys His Asn Met Leu Gly Gly Cys Pro 
                85                  90                  95      


Lys Glu Arg Ala Glu Ile Ser Met Leu Glu Gly Ala Val Leu Asp Ile 
            100                 105                 110         


Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser Lys Asp Phe Glu Thr Leu 
        115                 120                 125             


Lys Val Asp Phe Leu Ser Lys Leu Pro Glu Met Leu Lys Met Phe Glu 
    130                 135                 140                 


Asp Arg Leu Cys His Lys Thr Tyr Leu Asn Gly Asp His Val Thr His 
145                 150                 155                 160 


Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp Val Val Leu Tyr Met Asp 
                165                 170                 175     


Pro Met Cys Leu Asp Ala Phe Pro Lys Leu Val Cys Phe Lys Lys Arg 
            180                 185                 190         


Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr Leu Lys Ser Ser Lys Tyr 
        195                 200                 205             


Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala Thr Phe Gly Gly Gly Asp 
    210                 215                 220                 


His Pro Pro Lys Ser Asp Leu Val Pro Arg His Asn Gln Thr Ser Leu 
225                 230                 235                 240 


Tyr Lys Lys Ala Gly Phe Glu Gly Asp Arg Thr Met Lys Gln Lys Pro 
                245                 250                 255     


Arg Tyr Glu Ile Arg Trp Arg Val Ile Glu Ser Ile Ser Pro Asp Gly 
            260                 265                 270         


His Glu Tyr Ile Tyr Val Asp Pro Met Gln Leu Pro Tyr Asp Ser Arg 
        275                 280                 285             


Trp Glu Phe Pro Arg Asp Gly Leu Val Leu Gly Arg Val Leu Gly Ser 
    290                 295                 300                 


Gly Ala Phe Gly Lys Val Val Glu Gly Thr Ala Tyr Gly Leu Ser Arg 
305                 310                 315                 320 


Ser Gln Pro Val Met Lys Val Ala Val Lys Met Leu Lys Pro Thr Ala 
                325                 330                 335     


Arg Ser Ser Glu Lys Gln Ala Leu Met Ser Glu Leu Lys Ile Met Thr 
            340                 345                 350         


His Leu Gly Pro His Leu Asn Ile Val Asn Leu Leu Gly Ala Cys Thr 
        355                 360                 365             


Lys Ser Gly Pro Ile Tyr Ile Ile Thr Glu Tyr Cys Phe Tyr Gly Asp 
    370                 375                 380                 


Leu Val Asn Tyr Leu His Lys Asn Arg Asp Ser Phe Leu Ser His His 
385                 390                 395                 400 


Pro Glu Lys Pro Lys Lys Glu Leu Asp Ile Phe Gly Leu Asn Pro Ala 
                405                 410                 415     


Asp Glu Ser Thr Arg Ser Tyr Val Ile Leu Ser Phe Glu Asn Asn Gly 
            420                 425                 430         


Asp Tyr Met Asp Met Lys Gln Ala Asp Thr Thr Gln Tyr Val Pro Met 
        435                 440                 445             


Leu Glu Arg Lys Glu Val Ser Lys Tyr Ser Asp Ile Gln Arg Ser Leu 
    450                 455                 460                 


Tyr Asp Arg Pro Ala Ser Tyr Lys Lys Lys Ser Met Leu Asp Ser Glu 
465                 470                 475                 480 


Val Lys Asn Leu Leu Ser Asp Asp Asn Ser Glu Gly Leu Thr Leu Leu 
                485                 490                 495     


Asp Leu Leu Ser Phe Thr Tyr Gln Val Ala Arg Gly Met Glu Phe Leu 
            500                 505                 510         


Ala Ser Lys Asn Cys Val His Arg Asp Leu Ala Ala Arg Asn Val Leu 
        515                 520                 525             


Leu Ala Gln Gly Lys Ile Val Lys Ile Cys Asp Phe Gly Leu Ala Arg 
    530                 535                 540                 


Asp Ile Met His Asp Ser Asn Tyr Val Ser Lys Gly Ser Thr Phe Leu 
545                 550                 555                 560 


Pro Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asp Asn Leu Tyr Thr 
                565                 570                 575     


Thr Leu Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu Ile Phe 
            580                 585                 590         


Ser Leu Gly Gly Thr Pro Tyr Pro Gly Met Met Val Asp Ser Thr Phe 
        595                 600                 605             


Tyr Asn Lys Ile Lys Ser Gly Tyr Arg Met Ala Lys Pro Asp His Ala 
    610                 615                 620                 


Thr Ser Glu Val Tyr Glu Ile Met Val Lys Cys Trp Asn Ser Glu Pro 
625                 630                 635                 640 


Glu Lys Arg Pro Ser Phe Tyr His Leu Ser Glu Ile Val Glu Asn Leu 
                645                 650                 655     


Leu Pro Gly Gln Tyr Lys Lys Ser Tyr Glu Lys Ile His Leu Asp Phe 
            660                 665                 670         


Leu Lys Ser Asp His Pro Ala Val Ala Arg Met Arg Val Asp Ser Asp 
        675                 680                 685             


Asn Ala Tyr Ile Gly Val Thr Tyr Lys Asn Glu Glu Asp Lys Leu Lys 
    690                 695                 700                 


Asp Trp Glu Gly Gly Leu Asp Glu Gln Arg Leu Ser Ala Asp Ser Gly 
705                 710                 715                 720 


Tyr Ile Ile Pro Leu Pro Asp Ile Asp Pro Val Pro Glu Glu Glu Asp 
                725                 730                 735     


Leu Gly Lys Arg Asn Arg His Ser Ser Gln Thr Ser Glu Glu Ser Ala 
            740                 745                 750         


Ile Glu Thr Gly Ser Ser Ser Ser Thr Phe Ile Lys Arg Glu Asp Glu 
        755                 760                 765             


Thr Ile Glu Asp Ile Asp Met Met Asp Asp Ile Gly Ile Asp Ser Ser 
    770                 775                 780                 


Asp Leu Val Glu Asp Ser Phe Leu 
785                 790         


<210>  2
<211>  782
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ala Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys 
    50                  55                  60                  


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


His Asn Gln Thr Ser Leu Tyr Lys Lys Ala Gly Phe Glu Gly Asp Arg 
225                 230                 235                 240 


Thr Met Lys Gln Lys Pro Arg Tyr Glu Ile Arg Trp Arg Val Ile Glu 
                245                 250                 255     


Ser Ile Ser Pro Asp Gly His Glu Tyr Ile Tyr Val Asp Pro Met Gln 
            260                 265                 270         


Leu Pro Tyr Asp Ser Arg Trp Glu Phe Pro Arg Asp Gly Leu Val Leu 
        275                 280                 285             


Gly Arg Val Leu Gly Ser Gly Ala Phe Gly Lys Val Val Glu Gly Thr 
    290                 295                 300                 


Ala Tyr Gly Leu Ser Arg Ser Gln Pro Val Met Lys Val Ala Val Lys 
305                 310                 315                 320 


Met Leu Lys Pro Thr Ala Arg Ser Ser Glu Lys Gln Ala Leu Met Ser 
                325                 330                 335     


Glu Leu Lys Ile Met Thr His Leu Gly Pro His Leu Asn Ile Val Asn 
            340                 345                 350         


Leu Leu Gly Ala Cys Thr Lys Ser Gly Pro Ile Tyr Ile Ile Thr Glu 
        355                 360                 365             


Tyr Cys Phe Tyr Gly Asp Leu Val Asn Tyr Leu His Lys Asn Arg Asp 
    370                 375                 380                 


Ser Phe Leu Ser His His Pro Glu Lys Pro Lys Lys Glu Leu Asp Ile 
385                 390                 395                 400 


Phe Gly Leu Asn Pro Ala Asp Glu Ser Thr Arg Ser Tyr Val Ile Leu 
                405                 410                 415     


Ser Phe Glu Asn Asn Gly Asp Tyr Met Asp Met Lys Gln Ala Asp Thr 
            420                 425                 430         


Thr Gln Tyr Val Pro Met Leu Glu Arg Lys Glu Val Ser Lys Tyr Ser 
        435                 440                 445             


Asp Ile Gln Arg Ser Leu Tyr Asp Arg Pro Ala Ser Tyr Lys Lys Lys 
    450                 455                 460                 


Ser Met Leu Asp Ser Glu Val Lys Asn Leu Leu Ser Asp Asp Asn Ser 
465                 470                 475                 480 


Glu Gly Leu Thr Leu Leu Asp Leu Leu Ser Phe Thr Tyr Gln Val Ala 
                485                 490                 495     


Arg Gly Met Glu Phe Leu Ala Ser Lys Asn Cys Val His Arg Asp Leu 
            500                 505                 510         


Ala Ala Arg Asn Val Leu Leu Ala Gln Gly Lys Ile Val Lys Ile Cys 
        515                 520                 525             


Asp Phe Gly Leu Ala Arg Val Ile Met His Asp Ser Asn Tyr Val Ser 
    530                 535                 540                 


Lys Gly Ser Thr Phe Leu Pro Val Lys Trp Met Ala Pro Glu Ser Ile 
545                 550                 555                 560 


Phe Asp Asn Leu Tyr Thr Thr Leu Ser Asp Val Trp Ser Tyr Gly Ile 
                565                 570                 575     


Leu Leu Trp Glu Ile Phe Ser Leu Gly Gly Thr Pro Tyr Pro Gly Met 
            580                 585                 590         


Met Val Asp Ser Thr Phe Tyr Asn Lys Ile Lys Ser Gly Tyr Arg Met 
        595                 600                 605             


Ala Lys Pro Asp His Ala Thr Ser Glu Val Tyr Glu Ile Met Val Lys 
    610                 615                 620                 


Cys Trp Asn Ser Glu Pro Glu Lys Arg Pro Ser Phe Tyr His Leu Ser 
625                 630                 635                 640 


Glu Ile Val Glu Asn Leu Leu Pro Gly Gln Tyr Lys Lys Ser Tyr Glu 
                645                 650                 655     


Lys Ile His Leu Asp Phe Leu Lys Ser Asp His Pro Ala Val Ala Arg 
            660                 665                 670         


Met Arg Val Asp Ser Asp Asn Ala Tyr Ile Gly Val Thr Tyr Lys Asn 
        675                 680                 685             


Glu Glu Asp Lys Leu Lys Asp Trp Glu Gly Gly Leu Asp Glu Gln Arg 
    690                 695                 700                 


Leu Ser Ala Asp Ser Gly Tyr Ile Ile Pro Leu Pro Asp Ile Asp Pro 
705                 710                 715                 720 


Val Pro Glu Glu Glu Asp Leu Gly Lys Arg Asn Arg His Ser Ser Gln 
                725                 730                 735     


Thr Ser Glu Glu Ser Ala Ile Glu Thr Gly Ser Ser Ser Ser Thr Phe 
            740                 745                 750         


Ile Lys Arg Glu Asp Glu Thr Ile Glu Asp Ile Asp Met Met Asp Asp 
        755                 760                 765             


Ile Gly Ile Asp Ser Ser Asp Leu Val Glu Asp Ser Phe Leu 
    770                 775                 780         


<210>  3
<211>  802
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Glu His His His His His His His His Met Ala Pro Ile Leu Gly 
1               5                   10                  15      


Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro Thr Arg Leu Leu Leu Glu 
            20                  25                  30          


Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu Tyr Glu Arg Asp Glu Gly 
        35                  40                  45              


Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu Gly Leu Glu Phe Pro Asn 
    50                  55                  60                  


Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys Leu Thr Gln Ser Met Ala 
65                  70                  75                  80  


Ile Ile Arg Tyr Ile Ala Asp Lys His Asn Met Leu Gly Gly Cys Pro 
                85                  90                  95      


Lys Glu Arg Ala Glu Ile Ser Met Leu Glu Gly Ala Val Leu Asp Ile 
            100                 105                 110         


Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser Lys Asp Phe Glu Thr Leu 
        115                 120                 125             


Lys Val Asp Phe Leu Ser Lys Leu Pro Glu Met Leu Lys Met Phe Glu 
    130                 135                 140                 


Asp Arg Leu Cys His Lys Thr Tyr Leu Asn Gly Asp His Val Thr His 
145                 150                 155                 160 


Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp Val Val Leu Tyr Met Asp 
                165                 170                 175     


Pro Met Cys Leu Asp Ala Phe Pro Lys Leu Val Cys Phe Lys Lys Arg 
            180                 185                 190         


Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr Leu Lys Ser Ser Lys Tyr 
        195                 200                 205             


Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala Thr Phe Gly Gly Gly Asp 
    210                 215                 220                 


His Pro Pro Lys Ser Asp Leu Val Pro Arg His Asn Gln Thr Ser Leu 
225                 230                 235                 240 


Tyr Lys Lys Ala Gly Phe Glu Gly Asp Arg Thr Met Gln Lys Lys Pro 
                245                 250                 255     


Arg Tyr Glu Ile Arg Trp Lys Val Ile Glu Ser Val Ser Ser Asp Gly 
            260                 265                 270         


His Glu Tyr Ile Tyr Val Asp Pro Met Gln Leu Pro Tyr Asp Ser Thr 
        275                 280                 285             


Trp Glu Leu Pro Arg Asp Gln Leu Val Leu Gly Arg Thr Leu Gly Ser 
    290                 295                 300                 


Gly Ala Phe Gly Gln Val Val Glu Ala Thr Ala His Gly Leu Ser His 
305                 310                 315                 320 


Ser Gln Ala Thr Met Lys Val Ala Val Lys Met Leu Lys Ser Thr Ala 
                325                 330                 335     


Arg Ser Ser Glu Lys Gln Ala Leu Met Ser Glu Leu Lys Ile Met Ser 
            340                 345                 350         


His Leu Gly Pro His Leu Asn Val Val Asn Leu Leu Gly Ala Cys Thr 
        355                 360                 365             


Lys Gly Gly Pro Ile Tyr Ile Ile Thr Glu Tyr Cys Arg Tyr Gly Asp 
    370                 375                 380                 


Leu Val Asp Tyr Leu His Arg Asn Lys His Thr Phe Leu Gln His His 
385                 390                 395                 400 


Ser Asp Lys Arg Arg Pro Pro Ser Ala Glu Leu Tyr Ser Asn Ala Leu 
                405                 410                 415     


Pro Val Gly Leu Pro Leu Pro Ser His Val Ser Leu Thr Gly Glu Ser 
            420                 425                 430         


Asp Gly Gly Tyr Met Asp Met Ser Lys Asp Glu Ser Val Asp Tyr Val 
        435                 440                 445             


Pro Met Leu Asp Met Lys Gly Asp Val Lys Tyr Ala Asp Ile Glu Ser 
    450                 455                 460                 


Ser Asn Tyr Met Ala Pro Tyr Asp Asn Tyr Val Pro Ser Ala Pro Glu 
465                 470                 475                 480 


Arg Thr Cys Arg Ala Thr Leu Ile Asn Glu Ser Pro Val Leu Ser Tyr 
                485                 490                 495     


Met Asp Leu Val Gly Phe Ser Tyr Gln Val Ala Asn Gly Met Glu Phe 
            500                 505                 510         


Leu Ala Ser Lys Asn Cys Val His Arg Asp Leu Ala Ala Arg Asn Val 
        515                 520                 525             


Leu Ile Cys Glu Gly Lys Leu Val Lys Ile Cys Asp Phe Gly Leu Ala 
    530                 535                 540                 


Arg Asp Ile Met Arg Asp Ser Asn Tyr Ile Ser Lys Gly Ser Thr Phe 
545                 550                 555                 560 


Leu Pro Leu Lys Trp Met Ala Pro Glu Ser Ile Phe Asn Ser Leu Tyr 
                565                 570                 575     


Thr Thr Leu Ser Asp Val Trp Ser Phe Gly Ile Leu Leu Trp Glu Ile 
            580                 585                 590         


Phe Thr Leu Gly Gly Thr Pro Tyr Pro Glu Leu Pro Met Asn Glu Gln 
        595                 600                 605             


Phe Tyr Asn Ala Ile Lys Arg Gly Tyr Arg Met Ala Gln Pro Ala His 
    610                 615                 620                 


Ala Ser Asp Glu Ile Tyr Glu Ile Met Gln Lys Cys Trp Glu Glu Lys 
625                 630                 635                 640 


Phe Glu Ile Arg Pro Pro Phe Ser Gln Leu Val Leu Leu Leu Glu Arg 
                645                 650                 655     


Leu Leu Gly Glu Gly Tyr Lys Lys Lys Tyr Gln Gln Val Asp Glu Glu 
            660                 665                 670         


Phe Leu Arg Ser Asp His Pro Ala Ile Leu Arg Ser Gln Ala Arg Leu 
        675                 680                 685             


Pro Gly Phe His Gly Leu Arg Ser Pro Leu Asp Thr Ser Ser Val Leu 
    690                 695                 700                 


Tyr Thr Ala Val Gln Pro Asn Glu Gly Asp Lys Asp Tyr Ile Ile Pro 
705                 710                 715                 720 


Leu Pro Asp Pro Lys Pro Glu Val Ala Asp Glu Gly Pro Leu Glu Gly 
                725                 730                 735     


Ser Pro Ser Leu Ala Ser Ser Thr Leu Asn Glu Val Asn Thr Ser Ser 
            740                 745                 750         


Thr Ile Ser Cys Asp Ser Pro Leu Glu Pro Gln Asp Glu Pro Glu Pro 
        755                 760                 765             


Glu Pro Gln Leu Glu Leu Gln Val Glu Pro Glu Pro Glu Leu Glu Gln 
    770                 775                 780                 


Leu Pro Asp Ser Gly Cys Pro Ala Pro Arg Ala Glu Ala Glu Asp Ser 
785                 790                 795                 800 


Phe Leu 
        


