                         SEQUENCE LISTING

<110>  Array BioPharma, Inc.
 
<120>  MACROCYCLIC COMPOUNDS AS ROS1 KINASE INHIBITORS

<130>  46040-0005WO1

<150>  62/472,185
<151>  2017-03-16

<160>  1     

<170>  PatentIn version 3.5

<210>  1
<211>  2347
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Lys Asn Ile Tyr Cys Leu Ile Pro Lys Leu Val Asn Phe Ala Thr 
1               5                   10                  15      


Leu Gly Cys Leu Trp Ile Ser Val Val Gln Cys Thr Val Leu Asn Ser 
            20                  25                  30          


Cys Leu Lys Ser Cys Val Thr Asn Leu Gly Gln Gln Leu Asp Leu Gly 
        35                  40                  45              


Thr Pro His Asn Leu Ser Glu Pro Cys Ile Gln Gly Cys His Phe Trp 
    50                  55                  60                  


Asn Ser Val Asp Gln Lys Asn Cys Ala Leu Lys Cys Arg Glu Ser Cys 
65                  70                  75                  80  


Glu Val Gly Cys Ser Ser Ala Glu Gly Ala Tyr Glu Glu Glu Val Leu 
                85                  90                  95      


Glu Asn Ala Asp Leu Pro Thr Ala Pro Phe Ala Ser Ser Ile Gly Ser 
            100                 105                 110         


His Asn Met Thr Leu Arg Trp Lys Ser Ala Asn Phe Ser Gly Val Lys 
        115                 120                 125             


Tyr Ile Ile Gln Trp Lys Tyr Ala Gln Leu Leu Gly Ser Trp Thr Tyr 
    130                 135                 140                 


Thr Lys Thr Val Ser Arg Pro Ser Tyr Val Val Lys Pro Leu His Pro 
145                 150                 155                 160 


Phe Thr Glu Tyr Ile Phe Arg Val Val Trp Ile Phe Thr Ala Gln Leu 
                165                 170                 175     


Gln Leu Tyr Ser Pro Pro Ser Pro Ser Tyr Arg Thr His Pro His Gly 
            180                 185                 190         


Val Pro Glu Thr Ala Pro Leu Ile Arg Asn Ile Glu Ser Ser Ser Pro 
        195                 200                 205             


Asp Thr Val Glu Val Ser Trp Asp Pro Pro Gln Phe Pro Gly Gly Pro 
    210                 215                 220                 


Ile Leu Gly Tyr Asn Leu Arg Leu Ile Ser Lys Asn Gln Lys Leu Asp 
225                 230                 235                 240 


Ala Gly Thr Gln Arg Thr Ser Phe Gln Phe Tyr Ser Thr Leu Pro Asn 
                245                 250                 255     


Thr Ile Tyr Arg Phe Ser Ile Ala Ala Val Asn Glu Val Gly Glu Gly 
            260                 265                 270         


Pro Glu Ala Glu Ser Ser Ile Thr Thr Ser Ser Ser Ala Val Gln Gln 
        275                 280                 285             


Glu Glu Gln Trp Leu Phe Leu Ser Arg Lys Thr Ser Leu Arg Lys Arg 
    290                 295                 300                 


Ser Leu Lys His Leu Val Asp Glu Ala His Cys Leu Arg Leu Asp Ala 
305                 310                 315                 320 


Ile Tyr His Asn Ile Thr Gly Ile Ser Val Asp Val His Gln Gln Ile 
                325                 330                 335     


Val Tyr Phe Ser Glu Gly Thr Leu Ile Trp Ala Lys Lys Ala Ala Asn 
            340                 345                 350         


Met Ser Asp Val Ser Asp Leu Arg Ile Phe Tyr Arg Gly Ser Gly Leu 
        355                 360                 365             


Ile Ser Ser Ile Ser Ile Asp Trp Leu Tyr Gln Arg Met Tyr Phe Ile 
    370                 375                 380                 


Met Asp Glu Leu Val Cys Val Cys Asp Leu Glu Asn Cys Ser Asn Ile 
385                 390                 395                 400 


Glu Glu Ile Thr Pro Pro Ser Ile Ser Ala Pro Gln Lys Ile Val Ala 
                405                 410                 415     


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


Arg Ala Asp Leu Pro Val Pro Ser Gly Arg Cys Ala Glu Ala Val Arg 
        435                 440                 445             


Ile Val Glu Ser Cys Thr Leu Lys Asp Phe Ala Ile Lys Pro Gln Ala 
    450                 455                 460                 


Lys Arg Ile Ile Tyr Phe Asn Asp Thr Ala Gln Val Phe Met Ser Thr 
465                 470                 475                 480 


Phe Leu Asp Gly Ser Ala Ser His Leu Ile Leu Pro Arg Ile Pro Phe 
                485                 490                 495     


Ala Asp Val Lys Ser Phe Ala Cys Glu Asn Asn Asp Phe Leu Val Thr 
            500                 505                 510         


Asp Gly Lys Val Ile Phe Gln Gln Asp Ala Leu Ser Phe Asn Glu Phe 
        515                 520                 525             


Ile Val Gly Cys Asp Leu Ser His Ile Glu Glu Phe Gly Phe Gly Asn 
    530                 535                 540                 


Leu Val Ile Phe Gly Ser Ser Ser Gln Leu His Pro Leu Pro Gly Arg 
545                 550                 555                 560 


Pro Gln Glu Leu Ser Val Leu Phe Gly Ser His Gln Ala Leu Val Gln 
                565                 570                 575     


Trp Lys Pro Pro Ala Leu Ala Ile Gly Ala Asn Val Ile Leu Ile Ser 
            580                 585                 590         


Asp Ile Ile Glu Leu Phe Glu Leu Gly Pro Ser Ala Trp Gln Asn Trp 
        595                 600                 605             


Thr Tyr Glu Val Lys Val Ser Thr Gln Asp Pro Pro Glu Val Thr His 
    610                 615                 620                 


Ile Phe Leu Asn Ile Ser Gly Thr Met Leu Asn Val Pro Glu Leu Gln 
625                 630                 635                 640 


Ser Ala Met Lys Tyr Lys Val Ser Val Arg Ala Ser Ser Pro Lys Arg 
                645                 650                 655     


Pro Gly Pro Trp Ser Glu Pro Ser Val Gly Thr Thr Leu Val Pro Ala 
            660                 665                 670         


Ser Glu Pro Pro Phe Ile Met Ala Val Lys Glu Asp Gly Leu Trp Ser 
        675                 680                 685             


Lys Pro Leu Asn Ser Phe Gly Pro Gly Glu Phe Leu Ser Ser Asp Ile 
    690                 695                 700                 


Gly Asn Val Ser Asp Met Asp Trp Tyr Asn Asn Ser Leu Tyr Tyr Ser 
705                 710                 715                 720 


Asp Thr Lys Gly Asp Val Phe Val Trp Leu Leu Asn Gly Thr Asp Ile 
                725                 730                 735     


Ser Glu Asn Tyr His Leu Pro Ser Ile Ala Gly Ala Gly Ala Leu Ala 
            740                 745                 750         


Phe Glu Trp Leu Gly His Phe Leu Tyr Trp Ala Gly Lys Thr Tyr Val 
        755                 760                 765             


Ile Gln Arg Gln Ser Val Leu Thr Gly His Thr Asp Ile Val Thr His 
    770                 775                 780                 


Val Lys Leu Leu Val Asn Asp Met Val Val Asp Ser Val Gly Gly Tyr 
785                 790                 795                 800 


Leu Tyr Trp Thr Thr Leu Tyr Ser Val Glu Ser Thr Arg Leu Asn Gly 
                805                 810                 815     


Glu Ser Ser Leu Val Leu Gln Thr Gln Pro Trp Phe Ser Gly Lys Lys 
            820                 825                 830         


Val Ile Ala Leu Thr Leu Asp Leu Ser Asp Gly Leu Leu Tyr Trp Leu 
        835                 840                 845             


Val Gln Asp Ser Gln Cys Ile His Leu Tyr Thr Ala Val Leu Arg Gly 
    850                 855                 860                 


Gln Ser Thr Gly Asp Thr Thr Ile Thr Glu Phe Ala Ala Trp Ser Thr 
865                 870                 875                 880 


Ser Glu Ile Ser Gln Asn Ala Leu Met Tyr Tyr Ser Gly Arg Leu Phe 
                885                 890                 895     


Trp Ile Asn Gly Phe Arg Ile Ile Thr Thr Gln Glu Ile Gly Gln Lys 
            900                 905                 910         


Thr Ser Val Ser Val Leu Glu Pro Ala Arg Phe Asn Gln Phe Thr Ile 
        915                 920                 925             


Ile Gln Thr Ser Leu Lys Pro Leu Pro Gly Asn Phe Ser Phe Thr Pro 
    930                 935                 940                 


Lys Val Ile Pro Asp Ser Val Gln Glu Ser Ser Phe Arg Ile Glu Gly 
945                 950                 955                 960 


Asn Ala Ser Ser Phe Gln Ile Leu Trp Asn Gly Pro Pro Ala Val Asp 
                965                 970                 975     


Trp Gly Val Val Phe Tyr Ser Val Glu Phe Ser Ala His Ser Lys Phe 
            980                 985                 990         


Leu Ala Ser Glu Gln His Ser Leu  Pro Val Phe Thr Val  Glu Gly Leu 
        995                 1000                 1005             


Glu Pro  Tyr Ala Leu Phe Asn  Leu Ser Val Thr Pro  Tyr Thr Tyr 
    1010                 1015                 1020             


Trp Gly  Lys Gly Pro Lys Thr  Ser Leu Ser Leu Arg  Ala Pro Glu 
    1025                 1030                 1035             


Thr Val  Pro Ser Ala Pro Glu  Asn Pro Arg Ile Phe  Ile Leu Pro 
    1040                 1045                 1050             


Ser Gly  Lys Cys Cys Asn Lys  Asn Glu Val Val Val  Glu Phe Arg 
    1055                 1060                 1065             


Trp Asn  Lys Pro Lys His Glu  Asn Gly Val Leu Thr  Lys Phe Glu 
    1070                 1075                 1080             


Ile Phe  Tyr Asn Ile Ser Asn  Gln Ser Ile Thr Asn  Lys Thr Cys 
    1085                 1090                 1095             


Glu Asp  Trp Ile Ala Val Asn  Val Thr Pro Ser Val  Met Ser Phe 
    1100                 1105                 1110             


Gln Leu  Glu Gly Met Ser Pro  Arg Cys Phe Ile Ala  Phe Gln Val 
    1115                 1120                 1125             


Arg Ala  Phe Thr Ser Lys Gly  Pro Gly Pro Tyr Ala  Asp Val Val 
    1130                 1135                 1140             


Lys Ser  Thr Thr Ser Glu Ile  Asn Pro Phe Pro His  Leu Ile Thr 
    1145                 1150                 1155             


Leu Leu  Gly Asn Lys Ile Val  Phe Leu Asp Met Asp  Gln Asn Gln 
    1160                 1165                 1170             


Val Val  Trp Thr Phe Ser Ala  Glu Arg Val Ile Ser  Ala Val Cys 
    1175                 1180                 1185             


Tyr Thr  Ala Asp Asn Glu Met  Gly Tyr Tyr Ala Glu  Gly Asp Ser 
    1190                 1195                 1200             


Leu Phe  Leu Leu His Leu His  Asn Arg Ser Ser Ser  Glu Leu Phe 
    1205                 1210                 1215             


Gln Asp  Ser Leu Val Phe Asp  Ile Thr Val Ile Thr  Ile Asp Trp 
    1220                 1225                 1230             


Ile Ser  Arg His Leu Tyr Phe  Ala Leu Lys Glu Ser  Gln Asn Gly 
    1235                 1240                 1245             


Met Gln  Val Phe Asp Val Asp  Leu Glu His Lys Val  Lys Tyr Pro 
    1250                 1255                 1260             


Arg Glu  Val Lys Ile His Asn  Arg Asn Ser Thr Ile  Ile Ser Phe 
    1265                 1270                 1275             


Ser Val  Tyr Pro Leu Leu Ser  Arg Leu Tyr Trp Thr  Glu Val Ser 
    1280                 1285                 1290             


Asn Phe  Gly Tyr Gln Met Phe  Tyr Tyr Ser Ile Ile  Ser His Thr 
    1295                 1300                 1305             


Leu His  Arg Ile Leu Gln Pro  Thr Ala Thr Asn Gln  Gln Asn Lys 
    1310                 1315                 1320             


Arg Asn  Gln Cys Ser Cys Asn  Val Thr Glu Phe Glu  Leu Ser Gly 
    1325                 1330                 1335             


Ala Met  Ala Ile Asp Thr Ser  Asn Leu Glu Lys Pro  Leu Ile Tyr 
    1340                 1345                 1350             


Phe Ala  Lys Ala Gln Glu Ile  Trp Ala Met Asp Leu  Glu Gly Cys 
    1355                 1360                 1365             


Gln Cys  Trp Arg Val Ile Thr  Val Pro Ala Met Leu  Ala Gly Lys 
    1370                 1375                 1380             


Thr Leu  Val Ser Leu Thr Val  Asp Gly Asp Leu Ile  Tyr Trp Ile 
    1385                 1390                 1395             


Ile Thr  Ala Lys Asp Ser Thr  Gln Ile Tyr Gln Ala  Lys Lys Gly 
    1400                 1405                 1410             


Asn Gly  Ala Ile Val Ser Gln  Val Lys Ala Leu Arg  Ser Arg His 
    1415                 1420                 1425             


Ile Leu  Ala Tyr Ser Ser Val  Met Gln Pro Phe Pro  Asp Lys Ala 
    1430                 1435                 1440             


Phe Leu  Ser Leu Ala Ser Asp  Thr Val Glu Pro Thr  Ile Leu Asn 
    1445                 1450                 1455             


Ala Thr  Asn Thr Ser Leu Thr  Ile Arg Leu Pro Leu  Ala Lys Thr 
    1460                 1465                 1470             


Asn Leu  Thr Trp Tyr Gly Ile  Thr Ser Pro Thr Pro  Thr Tyr Leu 
    1475                 1480                 1485             


Val Tyr  Tyr Ala Glu Val Asn  Asp Arg Lys Asn Ser  Ser Asp Leu 
    1490                 1495                 1500             


Lys Tyr  Arg Ile Leu Glu Phe  Gln Asp Ser Ile Ala  Leu Ile Glu 
    1505                 1510                 1515             


Asp Leu  Gln Pro Phe Ser Thr  Tyr Met Ile Gln Ile  Ala Val Lys 
    1520                 1525                 1530             


Asn Tyr  Tyr Ser Asp Pro Leu  Glu His Leu Pro Pro  Gly Lys Glu 
    1535                 1540                 1545             


Ile Trp  Gly Lys Thr Lys Asn  Gly Val Pro Glu Ala  Val Gln Leu 
    1550                 1555                 1560             


Ile Asn  Thr Thr Val Arg Ser  Asp Thr Ser Leu Ile  Ile Ser Trp 
    1565                 1570                 1575             


Arg Glu  Ser His Lys Pro Asn  Gly Pro Lys Glu Ser  Val Arg Tyr 
    1580                 1585                 1590             


Gln Leu  Ala Ile Ser His Leu  Ala Leu Ile Pro Glu  Thr Pro Leu 
    1595                 1600                 1605             


Arg Gln  Ser Glu Phe Pro Asn  Gly Arg Leu Thr Leu  Leu Val Thr 
    1610                 1615                 1620             


Arg Leu  Ser Gly Gly Asn Ile  Tyr Val Leu Lys Val  Leu Ala Cys 
    1625                 1630                 1635             


His Ser  Glu Glu Met Trp Cys  Thr Glu Ser His Pro  Val Thr Val 
    1640                 1645                 1650             


Glu Met  Phe Asn Thr Pro Glu  Lys Pro Tyr Ser Leu  Val Pro Glu 
    1655                 1660                 1665             


Asn Thr  Ser Leu Gln Phe Asn  Trp Lys Ala Pro Leu  Asn Val Asn 
    1670                 1675                 1680             


Leu Ile  Arg Phe Trp Val Glu  Leu Gln Lys Trp Lys  Tyr Asn Glu 
    1685                 1690                 1695             


Phe Tyr  His Val Lys Thr Ser  Cys Ser Gln Gly Pro  Ala Tyr Val 
    1700                 1705                 1710             


Cys Asn  Ile Thr Asn Leu Gln  Pro Tyr Thr Ser Tyr  Asn Val Arg 
    1715                 1720                 1725             


Val Val  Val Val Tyr Lys Thr  Gly Glu Asn Ser Thr  Ser Leu Pro 
    1730                 1735                 1740             


Glu Ser  Phe Lys Thr Lys Ala  Gly Val Pro Asn Lys  Pro Gly Ile 
    1745                 1750                 1755             


Pro Lys  Leu Leu Glu Gly Ser  Lys Asn Ser Ile Gln  Trp Glu Lys 
    1760                 1765                 1770             


Ala Glu  Asp Asn Gly Cys Arg  Ile Thr Tyr Tyr Ile  Leu Glu Ile 
    1775                 1780                 1785             


Arg Lys  Ser Thr Ser Asn Asn  Leu Gln Asn Gln Asn  Leu Arg Trp 
    1790                 1795                 1800             


Lys Met  Thr Phe Asn Gly Ser  Cys Ser Ser Val Cys  Thr Trp Lys 
    1805                 1810                 1815             


Ser Lys  Asn Leu Lys Gly Ile  Phe Gln Phe Arg Val  Val Ala Ala 
    1820                 1825                 1830             


Asn Asn  Leu Gly Phe Gly Glu  Tyr Ser Gly Ile Ser  Glu Asn Ile 
    1835                 1840                 1845             


Ile Leu  Val Gly Asp Asp Phe  Trp Ile Pro Glu Thr  Ser Phe Ile 
    1850                 1855                 1860             


Leu Thr  Ile Ile Val Gly Ile  Phe Leu Val Val Thr  Ile Pro Leu 
    1865                 1870                 1875             


Thr Phe  Val Trp His Arg Arg  Leu Lys Asn Gln Lys  Ser Ala Lys 
    1880                 1885                 1890             


Glu Gly  Val Thr Val Leu Ile  Asn Glu Asp Lys Glu  Leu Ala Glu 
    1895                 1900                 1905             


Leu Arg  Gly Leu Ala Ala Gly  Val Gly Leu Ala Asn  Ala Cys Tyr 
    1910                 1915                 1920             


Ala Ile  His Thr Leu Pro Thr  Gln Glu Glu Ile Glu  Asn Leu Pro 
    1925                 1930                 1935             


Ala Phe  Pro Arg Glu Lys Leu  Thr Leu Arg Leu Leu  Leu Gly Ser 
    1940                 1945                 1950             


Gly Ala  Phe Gly Glu Val Tyr  Glu Gly Thr Ala Val  Asp Ile Leu 
    1955                 1960                 1965             


Gly Val  Gly Ser Gly Glu Ile  Lys Val Ala Val Lys  Thr Leu Lys 
    1970                 1975                 1980             


Lys Gly  Ser Thr Asp Gln Glu  Lys Ile Glu Phe Leu  Lys Glu Ala 
    1985                 1990                 1995             


His Leu  Met Ser Lys Phe Asn  His Pro Asn Ile Leu  Lys Gln Leu 
    2000                 2005                 2010             


Gly Val  Cys Leu Leu Asn Glu  Pro Gln Tyr Ile Ile  Leu Glu Leu 
    2015                 2020                 2025             


Met Glu  Gly Gly Asp Leu Leu  Thr Tyr Leu Arg Lys  Ala Arg Met 
    2030                 2035                 2040             


Ala Thr  Phe Tyr Gly Pro Leu  Leu Thr Leu Val Asp  Leu Val Asp 
    2045                 2050                 2055             


Leu Cys  Val Asp Ile Ser Lys  Gly Cys Val Tyr Leu  Glu Arg Met 
    2060                 2065                 2070             


His Phe  Ile His Arg Asp Leu  Ala Ala Arg Asn Cys  Leu Val Ser 
    2075                 2080                 2085             


Val Lys  Asp Tyr Thr Ser Pro  Arg Ile Val Lys Ile  Gly Asp Phe 
    2090                 2095                 2100             


Gly Leu  Ala Arg Asp Ile Tyr  Lys Asn Asp Tyr Tyr  Arg Lys Arg 
    2105                 2110                 2115             


Gly Glu  Gly Leu Leu Pro Val  Arg Trp Met Ala Pro  Glu Ser Leu 
    2120                 2125                 2130             


Met Asp  Gly Ile Phe Thr Thr  Gln Ser Asp Val Trp  Ser Phe Gly 
    2135                 2140                 2145             


Ile Leu  Ile Trp Glu Ile Leu  Thr Leu Gly His Gln  Pro Tyr Pro 
    2150                 2155                 2160             


Ala His  Ser Asn Leu Asp Val  Leu Asn Tyr Val Gln  Thr Gly Gly 
    2165                 2170                 2175             


Arg Leu  Glu Pro Pro Arg Asn  Cys Pro Asp Asp Leu  Trp Asn Leu 
    2180                 2185                 2190             


Met Thr  Gln Cys Trp Ala Gln  Glu Pro Asp Gln Arg  Pro Thr Phe 
    2195                 2200                 2205             


His Arg  Ile Gln Asp Gln Leu  Gln Leu Phe Arg Asn  Phe Phe Leu 
    2210                 2215                 2220             


Asn Ser  Ile Tyr Lys Ser Arg  Asp Glu Ala Asn Asn  Ser Gly Val 
    2225                 2230                 2235             


Ile Asn  Glu Ser Phe Glu Gly  Glu Asp Gly Asp Val  Ile Cys Leu 
    2240                 2245                 2250             


Asn Ser  Asp Asp Ile Met Pro  Val Ala Leu Met Glu  Thr Lys Asn 
    2255                 2260                 2265             


Arg Glu  Gly Leu Asn Tyr Met  Val Leu Ala Thr Glu  Cys Gly Gln 
    2270                 2275                 2280             


Gly Glu  Glu Lys Ser Glu Gly  Pro Leu Gly Ser Gln  Glu Ser Glu 
    2285                 2290                 2295             


Ser Cys  Gly Leu Arg Lys Glu  Glu Lys Glu Pro His  Ala Asp Lys 
    2300                 2305                 2310             


Asp Phe  Cys Gln Glu Lys Gln  Val Ala Tyr Cys Pro  Ser Gly Lys 
    2315                 2320                 2325             


Pro Glu  Gly Leu Asn Tyr Ala  Cys Leu Thr His Ser  Gly Tyr Gly 
    2330                 2335                 2340             


Asp Gly  Ser Asp 
    2345         


