                         SEQUENCE LISTING

<110>  Flynn, Daniel L.
       Kaufman, Michael D.
 
<120>  PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND 
       ANTI-PROLIFERATIVE ACTIVITIES

<130>  DECP-051/01US 313114-2291

<150>  US 61/562,602
<151>  2011-11-22

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  676
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  c-KIT with N-terminal CST fusion

<400>  1

Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro Thr Arg Leu Leu 
1               5                   10                  15      


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


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


Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys Leu Thr Gln Ser 
    50                  55                  60                  


Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn Met Leu Gly Gly 
65                  70                  75                  80  


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


Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser Lys Asp Phe Glu Thr 
            100                 105                 110         


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


Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn Gly Asp His Val Thr 
    130                 135                 140                 


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


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


Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr Leu Lys Ser Ser Lys 
            180                 185                 190         


Tyr Ile Trp Pro Leu Gln Gly Trp Gln Ala Thr Phe Gly Gly Gly Asp 
        195                 200                 205             


His Pro Pro Lys Ser Asp Leu Val Pro Arg His Asn Gln Thr Ser Leu 
    210                 215                 220                 


Tyr Lys Lys Ala Gly Ser Ala Ala Ala Val Leu Glu Glu Asn Leu Tyr 
225                 230                 235                 240 


Phe Gln Gly Thr Tyr Lys Tyr Leu Gln Lys Pro Met Tyr Glu Val Gln 
                245                 250                 255     


Trp Lys Val Val Glu Glu Ile Asn Gly Asn Asn Tyr Val Tyr Ile Asp 
            260                 265                 270         


Pro Thr Gln Leu Pro Tyr Asp His Lys Trp Glu Phe Pro Arg Asn Arg 
        275                 280                 285             


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


Glu Ala Thr Ala Tyr Gly Leu Ile Lys Ser Asp Ala Ala Met Thr Val 
305                 310                 315                 320 


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


Leu Met Ser Glu Leu Lys Val Leu Ser Tyr Leu Gly Asn His Met Asn 
            340                 345                 350         


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


Ile Thr Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Phe Leu Arg Arg 
    370                 375                 380                 


Lys Arg Asp Ser Phe Ile Cys Ser Lys Gln Glu Asp His Ala Glu Ala 
385                 390                 395                 400 


Ala Leu Tyr Lys Asn Leu Leu His Ser Lys Glu Ser Ser Cys Ser Asp 
                405                 410                 415     


Ser Thr Asn Glu Tyr Met Asp Met Lys Pro Gly Val Ser Tyr Val Val 
            420                 425                 430         


Pro Thr Lys Ala Asp Lys Arg Arg Ser Val Arg Ile Gly Ser Tyr Ile 
        435                 440                 445             


Glu Arg Asp Val Thr Pro Ala Ile Met Glu Asp Asp Glu Leu Ala Leu 
    450                 455                 460                 


Asp Leu Glu Asp Leu Leu Ser Phe Ser Tyr Gln Val Ala Lys Gly Met 
465                 470                 475                 480 


Ala Phe Leu Ala Ser Lys Asn Cys Ile His Arg Asp Leu Ala Ala Arg 
                485                 490                 495     


Asn Ile Leu Leu Thr His Gly Arg Ile Thr Lys Ile Cys Asp Phe Gly 
            500                 505                 510         


Leu Ala Arg Asp Ile Lys Asn Asp Ser Asn Tyr Val Val Lys Gly Asn 
        515                 520                 525             


Ala Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asn Cys 
    530                 535                 540                 


Val Tyr Thr Phe Glu Ser Asp Val Trp Ser Tyr Gly Ile Phe Leu Trp 
545                 550                 555                 560 


Glu Leu Phe Ser Leu Gly Ser Ser Pro Tyr Pro Gly Met Pro Val Asp 
                565                 570                 575     


Ser Lys Phe Tyr Lys Met Ile Lys Glu Gly Phe Arg Met Leu Ser Pro 
            580                 585                 590         


Glu His Ala Pro Ala Glu Met Tyr Asp Ile Met Lys Thr Cys Trp Asp 
        595                 600                 605             


Ala Asp Pro Leu Lys Arg Pro Thr Phe Lys Gln Ile Val Gln Leu Ile 
    610                 615                 620                 


Glu Lys Gln Ile Ser Glu Ser Thr Asn His Ile Tyr Ser Asn Leu Ala 
625                 630                 635                 640 


Asn Cys Ser Pro Asn Arg Gln Lys Pro Val Val Asp His Ser Val Arg 
                645                 650                 655     


Ile Asn Ser Val Gly Ser Thr Ala Ser Ser Ser Gln Pro Leu Leu Val 
            660                 665                 670         


His Asp Asp Val 
        675     


<210>  2
<211>  474
<212>  PRT
<213>  Unknown

<220>
<223>  c-MET kinase

<400>  2

Met Ser Tyr Tyr His His His His His His Asp Tyr Asp Ile Pro Thr 
1               5                   10                  15      


Thr Glu Asn Leu Tyr Phe Gln Gly Ala Met Leu Val Pro Arg Gly Ser 
            20                  25                  30          


Pro Trp Ile Pro Phe Thr Met Lys Lys Arg Lys Gln Ile Lys Asp Leu 
        35                  40                  45              


Gly Ser Glu Leu Val Arg Tyr Asp Ala Arg Val His Thr Pro His Leu 
    50                  55                  60                  


Asp Arg Leu Val Ser Ala Arg Ser Val Ser Pro Thr Thr Glu Met Val 
65                  70                  75                  80  


Ser Asn Glu Ser Val Asp Tyr Arg Ala Thr Phe Pro Glu Asp Gln Phe 
                85                  90                  95      


Pro Asn Ser Ser Gln Asn Gly Ser Cys Arg Gln Val Gln Tyr Pro Leu 
            100                 105                 110         


Thr Asp Met Ser Pro Ile Leu Thr Ser Gly Asp Ser Asp Ile Ser Ser 
        115                 120                 125             


Pro Leu Leu Gln Asn Thr Val His Ile Asp Leu Ser Ala Leu Asn Pro 
    130                 135                 140                 


Glu Leu Val Gln Ala Val Gln His Val Val Ile Gly Pro Ser Ser Leu 
145                 150                 155                 160 


Ile Val His Phe Asn Glu Val Ile Gly Arg Gly His Phe Gly Cys Val 
                165                 170                 175     


Tyr His Gly Thr Leu Leu Asp Asn Asp Gly Lys Lys Ile His Cys Ala 
            180                 185                 190         


Val Lys Ser Leu Asn Arg Ile Thr Asp Ile Gly Glu Val Ser Gln Phe 
        195                 200                 205             


Leu Thr Glu Gly Ile Ile Met Lys Asp Phe Ser His Pro Asn Val Leu 
    210                 215                 220                 


Ser Leu Leu Gly Ile Cys Leu Arg Ser Glu Gly Ser Pro Leu Val Val 
225                 230                 235                 240 


Leu Pro Tyr Met Lys His Gly Asp Leu Arg Asn Phe Ile Arg Asn Glu 
                245                 250                 255     


Thr His Asn Pro Thr Val Lys Asp Leu Ile Gly Phe Gly Leu Gln Val 
            260                 265                 270         


Ala Lys Gly Met Lys Tyr Leu Ala Ser Lys Lys Phe Val His Arg Asp 
        275                 280                 285             


Leu Ala Ala Arg Asn Cys Met Leu Asp Glu Lys Phe Thr Val Lys Val 
    290                 295                 300                 


Ala Asp Phe Gly Leu Ala Arg Asp Met Tyr Asp Lys Glu Tyr Tyr Ser 
305                 310                 315                 320 


Val His Asn Lys Thr Gly Ala Lys Leu Pro Val Lys Trp Met Ala Leu 
                325                 330                 335     


Glu Ser Leu Gln Thr Gln Lys Phe Thr Thr Lys Ser Asp Val Trp Ser 
            340                 345                 350         


Phe Gly Val Leu Leu Trp Glu Leu Met Thr Arg Gly Ala Pro Pro Tyr 
        355                 360                 365             


Pro Asp Val Asn Thr Phe Asp Ile Thr Val Tyr Leu Leu Gln Gly Arg 
    370                 375                 380                 


Arg Leu Leu Gln Pro Glu Tyr Cys Pro Asp Pro Leu Tyr Glu Val Met 
385                 390                 395                 400 


Leu Lys Cys Trp His Pro Lys Ala Glu Met Arg Pro Ser Phe Ser Glu 
                405                 410                 415     


Leu Val Ser Arg Ile Ser Ala Ile Phe Ser Thr Phe Ile Gly Glu His 
            420                 425                 430         


Tyr Val His Val Asn Ala Thr Tyr Val Asn Val Lys Cys Val Ala Pro 
        435                 440                 445             


Tyr Pro Ser Leu Leu Ser Ser Glu Asp Asn Ala Asp Asp Glu Val Asp 
    450                 455                 460                 


Thr Arg Pro Ala Ser Phe Trp Glu Thr Ser 
465                 470                 


<210>  3
<211>  315
<212>  PRT
<213>  Unknown

<220>
<223>  KDR protein sequence used for screening

<400>  3

Asp Pro Asp Glu Leu Pro Leu Asp Glu His Cys Glu Arg Leu Pro Tyr 
1               5                   10                  15      


Asp Ala Ser Lys Trp Glu Phe Pro Arg Asp Arg Leu Lys Leu Gly Lys 
            20                  25                  30          


Pro Leu Gly Arg Gly Ala Phe Gly Gln Val Ile Glu Ala Asp Ala Phe 
        35                  40                  45              


Gly Ile Asp Lys Thr Ala Thr Cys Arg Thr Val Ala Val Lys Met Leu 
    50                  55                  60                  


Lys Glu Gly Ala Thr His Ser Glu His Arg Ala Leu Met Ser Glu Leu 
65                  70                  75                  80  


Lys Ile Leu Ile His Ile Gly His His Leu Asn Val Val Asn Leu Leu 
                85                  90                  95      


Gly Ala Cys Thr Lys Pro Gly Gly Pro Leu Met Val Ile Val Glu Phe 
            100                 105                 110         


Cys Lys Phe Gly Asn Leu Ser Thr Tyr Leu Arg Ser Lys Arg Asn Glu 
        115                 120                 125             


Phe Val Pro Tyr Lys Val Ala Pro Glu Asp Leu Tyr Lys Asp Phe Leu 
    130                 135                 140                 


Thr Leu Glu His Leu Ile Cys Tyr Ser Phe Gln Val Ala Lys Gly Met 
145                 150                 155                 160 


Glu Phe Leu Ala Ser Arg Lys Cys Ile His Arg Asp Leu Ala Ala Arg 
                165                 170                 175     


Asn Ile Leu Leu Ser Glu Lys Asn Val Val Lys Ile Cys Asp Phe Gly 
            180                 185                 190         


Leu Ala Arg Asp Ile Tyr Lys Asp Pro Asp Tyr Val Arg Lys Gly Asp 
        195                 200                 205             


Ala Arg Leu Pro Leu Lys Trp Met Ala Pro Glu Thr Ile Phe Asp Arg 
    210                 215                 220                 


Val Tyr Thr Ile Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp 
225                 230                 235                 240 


Glu Ile Phe Ser Leu Gly Ala Ser Pro Tyr Pro Gly Val Lys Ile Asp 
                245                 250                 255     


Glu Glu Phe Cys Arg Arg Leu Lys Glu Gly Thr Arg Met Arg Ala Pro 
            260                 265                 270         


Asp Tyr Thr Thr Pro Glu Met Tyr Gln Thr Met Leu Asp Cys Trp His 
        275                 280                 285             


Gly Glu Pro Ser Gln Arg Pro Thr Phe Ser Glu Leu Val Glu His Leu 
    290                 295                 300                 


Gly Asn Leu Leu Gln Ala Asn Ala Gln Gln Asp 
305                 310                 315 


<210>  4
<211>  435
<212>  PRT
<213>  Unknown

<220>
<223>  cFMS protein sequence used for screening

<400>  4

Tyr Lys Tyr Lys Gln Lys Pro Lys Tyr Gln Val Arg Trp Lys Ile Ile 
1               5                   10                  15      


Glu Ser Tyr Glu Gly Asn Ser Tyr Thr Phe Ile Asp Pro Thr Gln Leu 
            20                  25                  30          


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


Lys Thr Leu Gly Ala Gly Ala Phe Gly Lys Val Val Glu Ala Thr Ala 
    50                  55                  60                  


Phe Gly Leu Gly Lys Glu Asp Ala Val Leu Lys Val Ala Val Lys Met 
65                  70                  75                  80  


Leu Lys Ser Thr Ala His Ala Asp Glu Lys Glu Ala Leu Met Ser Glu 
                85                  90                  95      


Leu Lys Ile Met Ser His Leu Gly Gln His Glu Asn Ile Val Asn Leu 
            100                 105                 110         


Leu Gly Ala Cys Thr His Gly Gly Pro Val Leu Val Ile Thr Glu Tyr 
        115                 120                 125             


Cys Cys Tyr Gly Asp Leu Leu Asn Phe Leu Arg Arg Lys Ala Glu Ala 
    130                 135                 140                 


Met Leu Gly Pro Ser Leu Ser Pro Gly Gln Asp Pro Glu Gly Gly Val 
145                 150                 155                 160 


Asp Tyr Lys Asn Ile His Leu Glu Lys Lys Tyr Val Arg Arg Asp Ser 
                165                 170                 175     


Gly Phe Ser Ser Gln Gly Val Asp Thr Tyr Val Glu Met Arg Pro Val 
            180                 185                 190         


Ser Thr Ser Ser Asn Asp Ser Phe Ser Glu Gln Asp Leu Asp Lys Glu 
        195                 200                 205             


Asp Gly Arg Pro Leu Glu Leu Arg Asp Leu Leu His Phe Ser Ser Gln 
    210                 215                 220                 


Val Ala Gln Gly Met Ala Phe Leu Ala Ser Lys Asn Cys Ile His Arg 
225                 230                 235                 240 


Asp Val Ala Ala Arg Asn Val Leu Leu Thr Asn Gly His Val Ala Lys 
                245                 250                 255     


Ile Gly Asp Phe Gly Leu Ala Arg Asp Ile Met Asn Asp Ser Asn Tyr 
            260                 265                 270         


Ile Val Lys Gly Asn Ala Arg Leu Pro Val Lys Trp Met Ala Pro Glu 
        275                 280                 285             


Ser Ile Phe Asp Cys Val Tyr Thr Val Gln Ser Asp Val Trp Ser Tyr 
    290                 295                 300                 


Gly Ile Leu Leu Trp Glu Ile Phe Ser Leu Gly Leu Asn Pro Tyr Pro 
305                 310                 315                 320 


Gly Ile Leu Val Asn Ser Lys Phe Tyr Lys Leu Val Lys Asp Gly Tyr 
                325                 330                 335     


Gln Met Ala Gln Pro Ala Phe Ala Pro Lys Asn Ile Tyr Ser Ile Met 
            340                 345                 350         


Gln Ala Cys Trp Ala Leu Glu Pro Thr His Arg Pro Thr Phe Gln Gln 
        355                 360                 365             


Ile Cys Ser Phe Leu Gln Glu Gln Ala Gln Glu Asp Arg Arg Glu Arg 
    370                 375                 380                 


Asp Tyr Thr Asn Leu Pro Ser Ser Ser Arg Ser Gly Gly Ser Gly Ser 
385                 390                 395                 400 


Ser Ser Ser Glu Leu Glu Glu Glu Ser Ser Ser Glu His Leu Thr Cys 
                405                 410                 415     


Cys Glu Gln Gly Asp Ile Ala Gln Pro Leu Leu Gln Pro Asn Asn Tyr 
            420                 425                 430         


Gln Phe Cys 
        435 


