Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T57700 | Target Info | |||
| Target Name | Tyrosine-protein kinase Kit (KIT) | ||||
| Synonyms | v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; p145 c-kit; Proto-oncogene tyrosine-protein kinase Kit; Proto-oncogene c-Kit; Piebald trait protein; PBT; Mast/stem cell growth factor receptor Kit; CD117 antigen; CD117; C-kit | ||||
| Target Type | Successful Target | ||||
| Gene Name | KIT | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Sunitinib | Ligand Info | |||||
| Structure Description | KIT kinase domain in complex with sunitinib | PDB:3G0E | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [1] |
| PDB Sequence |
GPTYKYLQKP
551 MYEVQWKVVE561 EINGNNYVYI571 DPTQLPYDHK581 WEFPRNRLSF591 GKTLGAGAFG 601 KVVEATAYGL611 IKSDAAMTVA621 VKMLKPSAHL631 TEREALMSEL641 KVLSYLGNHM 651 NIVNLLGACT661 IGGPTLVITE671 YCCYGDLLNF681 LRRKRDSFIC691 SKTSPAIMED 759 DELALDLEDL769 LSFSYQVAKG779 MAFLASKNCI789 HRDLAARNIL799 LTHGRITKIC 809 DFGLARDIKN819 DSNYVVKGNA829 RLPVKWMAPE839 SIFNCVYTFE849 SDVWSYGIFL 859 WELFSLGSSP869 YPGMPVDSKF879 YKMIKEGFRM889 LSPEHAPAEM899 YDIMKTCWDA 909 DPLKRPTFKQ919 IVQLIEKQIS929 ES
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LYS593
4.447
LEU595
3.252
GLY596
4.884
VAL603
3.499
ALA621
3.365
LYS623
4.151
VAL654
3.926
THR670
3.324
GLU671
2.979
TYR672
3.555
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Pexidartinib | Ligand Info | |||||
| Structure Description | Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX3397 | PDB:7KHG | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [2] |
| PDB Sequence |
HHHMPMYEVQ
556 WKVVEESNGN566 NYSYIDPTQL576 PYDHKWEFPR586 NRLSFGKTLG596 AGAFGKVVEA 606 TAQGLIKSDA616 AMTVAVKMLK626 PSAHSTEREA636 LMSELKVLSY646 LGNHENIVNL 656 LGACTHGGPT666 LVITEYCCYG676 DLLNFLRRKR686 DSFHSSDTSP754 ASMEDDENAL 764 DLEDLLSFSY774 QVAKGMAFLA784 SKNCIHRDLA794 ARNILLTHGR804 ITKICDFGLA 814 RDIKNDSNYV824 DKGNARLPVK834 WMAPESIFNS844 VYTFESDVWS854 YGIFLWELFS 864 LGSSPYPGMP874 VDSKFYKMIK884 EGFRMSSPEH894 APAEMYDIMK904 TCWDADPDKR 914 PTFKQIVQDI924 EKQISES
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TRP557
3.193
LEU595
3.843
VAL603
3.843
ALA621
3.442
LYS623
3.698
GLU640
3.020
LEU644
3.993
LEU647
4.326
ILE653
3.286
VAL654
3.625
THR670
3.568
GLU671
2.872
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| Ligand Name: Ponatinib | Ligand Info | |||||
| Structure Description | Crystal structure of KIT in complex with ponatinib | PDB:4U0I | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
GNNYVYIDPT
574 QLPYDHKWEF584 PRNRLSFGKT594 LGAGAFGKVV604 EATAYGLIAA617 MTVAVKMLKP 627 SAHLTEREAL637 MSELKVLSYL647 GNHMNIVNLL657 GACTIGGPTL667 VITEYCCYGD 677 LLNFLRRKRD687 SFICSLALDL766 EDLLSFSYQV776 AKGMAFLASK786 NCIHRDLAAR 796 NILLTHGRIT806 KICDFGLARD816 IKNDSNYVVK826 GNARLPVKWM836 APESIFNCVY 846 TFESDVWSYG856 IFLWELFSLG866 SSPYPGMPVD876 SKFYKMIKEG886 FRMLSPEHAP 896 AEMYDIMKTC906 WDADPLKRPT916 FKQIVQLIEK926 QISESTN
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0LI or .0LI2 or .0LI3 or :30LI;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:670 or .A:671 or .A:672 or .A:673 or .A:676 or .A:677 or .A:783 or .A:788 or .A:789 or .A:790 or .A:791 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.684
VAL603
3.899
ALA621
3.436
VAL622
3.426
LYS623
3.258
GLU640
2.652
VAL643
4.189
LEU644
3.807
LEU647
3.187
ILE653
3.587
VAL654
3.436
VAL668
3.720
THR670
3.431
GLU671
3.396
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| Ligand Name: Imatinib | Ligand Info | |||||
| Structure Description | STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE | PDB:1T46 | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [4] |
| PDB Sequence |
GNNYVYIDPT
574 QLPYDHKWEF584 PRNRLSFGKT594 LGAGAFGKVV604 EATAYGLIKS614 DAAMTVAVKM 624 LKPSAHLTER634 EALMSELKVL644 SYLGNHMNIV654 NLLGACTIGG664 PTLVITEYCC 674 YGDLLNFLRR684 KRDSFLALDL766 EDLLSFSYQV776 AKGMAFLASK786 NCIHRDLAAR 796 NILLTHGRIT806 KICDFGLARD816 IKNDSNYVVK826 GNARLPVKWM836 APESIFNCVY 846 TFESDVWSYG856 IFLWELFSLG866 SSPYPGMPVD876 SKFYKMIKEG886 FRMLSPEHAP 896 AEMYDIMKTC906 WDADPLKRPT916 FKQIVQLIEK926 QISESTN
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .STI or .STI2 or .STI3 or :3STI;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:669 or .A:670 or .A:671 or .A:672 or .A:673 or .A:676 or .A:677 or .A:783 or .A:788 or .A:789 or .A:790 or .A:791 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.775
VAL603
3.773
ALA621
3.582
VAL622
3.778
LYS623
3.392
GLU640
2.862
VAL643
3.839
LEU644
3.324
LEU647
4.075
ILE653
4.900
VAL654
3.899
VAL668
3.619
ILE669
4.935
THR670
2.950
GLU671
4.294
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| Ligand Name: Phosphonotyrosine | Ligand Info | |||||
| Structure Description | Crystal structure of activated c-KIT in complex with compound | PDB:6ITV | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | No | [5] |
| PDB Sequence |
VIDPTQLPYD
579 HKWEFPRNRL589 SFGKTLGAGA599 FGKVVEATAY609 GLIKSDAAMT619 VAVKMLKPSA 629 HLTEREALMS639 ELKVLSYLGN649 HMNIVNLLGA659 CTIGGPTLVI669 TEYCCYGDLL 679 NFLRRKRDSE758 DDELALDLED768 LLSFSYQVAK778 GMAFLASKNC788 IHRDLAARNI 798 LLTHGRITKI808 CDFGLARDIK818 NDSNYVVKGN828 ARLPVKWMAP838 ESIFNCVYTF 848 ESDVWSYGIF858 LWELFSLGSS868 PYPGMPVDSK878 FYKMIKEGFR888 MLSPEHAPAE 898 MYDIMKTCWD908 ADPLKRPTFK918 QIVQLIEKQI928 SESTNHI
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PTR or .PTR2 or .PTR3 or :3PTR;style chemicals stick;color identity;select .A:569 or .A:571 or .A:572 or .A:787 or .A:789 or .A:846 or .A:847 or .A:848 or .A:849; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Structure of a c-Kit Kinase Product Complex | PDB:1PKG | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | Yes | [6] |
| PDB Sequence |
NVIDPTQLPY
578 DHKWEFPRNR588 LSFGKTLGAG598 AFGKVVEATA608 YGLIKSDAAM618 TVAVKMLKPS 628 AHLTEREALM638 SELKVLSYLG648 NHMNIVNLLG658 ACTIGGPTLV668 ITEYCCYGDL 678 LNFLRRKRDS688 FICSKALDLE767 DLLSFSYQVA777 KGMAFLASKN787 CIHRDLAARN 797 ILLTHGRITK807 ICDFGLARDI817 KNDSNYVVKG827 NARLPVKWMA837 PESIFNCVYT 847 FESDVWSYGI857 FLWELFSLGS867 SPYPGMPVDS877 KFYKMIKEGF887 RMLSPEHAPA 897 EMYDIMKTCW907 DADPLKRPTF917 KQIVQLIEKQ927
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ADP or .ADP2 or .ADP3 or :3ADP;style chemicals stick;color identity;select .A:595 or .A:596 or .A:597 or .A:598 or .A:599 or .A:600 or .A:601 or .A:602 or .A:603 or .A:621 or .A:623 or .A:640 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:676 or .A:677 or .A:796 or .A:797 or .A:799 or .A:809 or .A:810; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.748
GLY596
3.561
ALA597
3.944
GLY598
2.674
ALA599
3.428
PHE600
3.290
GLY601
2.858
LYS602
4.946
VAL603
3.474
ALA621
3.381
LYS623
2.709
GLU640
4.588
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| Ligand Name: 5-(1h-Pyrrolo[2,3-B]pyridin-3-Ylmethyl)-N-[4-(Trifluoromethyl)benzyl]pyridin-2-Amine | Ligand Info | |||||
| Structure Description | Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX647 | PDB:4HVS | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [7] |
| PDB Sequence |
HHMPMYEVQW
557 KVVEESNGNN567 YSYIDPTQLP577 YDHKWEFPRN587 RLSFGKTLGA597 GAFGKVVEAT 607 AQGLIKSDAA617 MTVAVKMLKP627 SAHSTEREAL637 MSELKVLSYL647 GNHENIVNLL 657 GACTHGGPTL667 VITEYCCYGD677 LLNFLRRKRD687 SFHSSDTSPA755 SMEDDENALD 765 LEDLLSFSYQ775 VAKGMAFLAS785 KNCIHRDLAA795 RNILLTHGRI805 TKICDFGLAR 815 DIKNDSNYVD825 KGNARLPVKW835 MAPESIFNSV845 YTFESDVWSY855 GIFLWELFSL 865 GSSPYPGMPV875 DSKFYKMIKE885 GFRMSSPEHA895 PAEMYDIMKT905 CWDADPDKRP 915 TFKQIVQDIE925 KQISES
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .647 or .6472 or .6473 or :3647;style chemicals stick;color identity;select .A:557 or .A:595 or .A:603 or .A:621 or .A:623 or .A:640 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:676 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TRP557
3.331
LEU595
3.729
VAL603
3.819
ALA621
3.465
LYS623
3.655
GLU640
3.118
LEU644
3.984
LEU647
3.699
ILE653
3.396
VAL654
3.577
THR670
3.577
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| Ligand Name: Bezuclastinib | Ligand Info | |||||
| Structure Description | Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX9486 (bezuclastinib) in the DFG-in state | PDB:7KHK | ||||
| Method | X-ray diffraction | Resolution | 2.34 Å | Mutation | No | [2] |
| PDB Sequence |
NNYSYIDPTQ
575 LPYDHKWEFP585 RNRLSFGKTL595 GAGAFGKVVE605 ATAQGLIKSD615 AAMTVAVKML 625 KPSTEREALM638 SELKVLSYLG648 NHENIVNLLG658 ACTHGGPTLV668 ITEYCCYGDL 678 LNFLRRKRDS688 FHENALDLED768 LLSFSYQVAK778 GMAFLASKNC788 IHRDLAARNI 798 LLTHGRITKI808 CDFGLARVIK818 NDSNYVDKAR830 LPVKWMAPES840 IFNSVYTFES 850 DVWSYGIFLW860 ELFSLGSSPY870 PGMPVDSKFY880 KMIKEGFRMS890 SPEHAPAEMY 900 DIMKTCWDAD910 PDKRPTFKQI920 VQDIEKQISE930 S
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .WEJ or .WEJ2 or .WEJ3 or :3WEJ;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:644 or .A:654 or .A:668 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:799 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.397
VAL603
3.826
ALA621
3.611
VAL622
4.575
LYS623
3.415
GLU640
2.697
LEU644
4.101
VAL654
4.192
VAL668
3.492
THR670
3.036
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| Ligand Name: 2-phenyl-5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine | Ligand Info | |||||
| Structure Description | Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX8512 in the DFG-in state | PDB:7KHJ | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [2] |
| PDB Sequence |
NNYSYIDPTQ
575 LPYDHKWEFP585 RNRLSFGKTL595 GAGGKVVEAT607 AQGLIKSDAA617 MTVAVKMLKP 627 STEREALMSE640 LKVLSYLGNH650 ENIVNLLGAC660 THGGPTLVIT670 EYCCYGDLLN 680 FLRRKRDSFH690 NALDLEDLLS771 FSYQVAKGMA781 FLASKNCIHR791 DLAARNILLT 801 HGRITKICDF811 GLARVIKNDS821 NYVDKARLPV833 KWMAPESIFN843 SVYTFESDVW 853 SYGIFLWELF863 SLGSSPYPGM873 PVDSKFYKMI883 KEGFRMSSPE893 HAPAEMYDIM 903 KTCWDADPDK913 RPTFKQIVQD923 IEKQISES
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .WEG or .WEG2 or .WEG3 or :3WEG;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:623 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:799 or .A:809 or .A:810; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-(5-ethyl-1,2-oxazol-3-yl)-N'-[4-(2-{[6-(4-ethylpyrazin-1(4H)-yl)pyrimidin-4-yl]amino}-1,3-thiazol-5-yl)phenyl]urea | Ligand Info | |||||
| Structure Description | Crystal structure of activated c-KIT in complex with compound | PDB:6ITV | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | No | [5] |
| PDB Sequence |
VIDPTQLPYD
579 HKWEFPRNRL589 SFGKTLGAGA599 FGKVVEATAY609 GLIKSDAAMT619 VAVKMLKPSA 629 HLTEREALMS639 ELKVLSYLGN649 HMNIVNLLGA659 CTIGGPTLVI669 TEYCCYGDLL 679 NFLRRKRDSE758 DDELALDLED768 LLSFSYQVAK778 GMAFLASKNC788 IHRDLAARNI 798 LLTHGRITKI808 CDFGLARDIK818 NDSNYVVKGN828 ARLPVKWMAP838 ESIFNCVYTF 848 ESDVWSYGIF858 LWELFSLGSS868 PYPGMPVDSK878 FYKMIKEGFR888 MLSPEHAPAE 898 MYDIMKTCWD908 ADPLKRPTFK918 QIVQLIEKQI928 SESTNHI
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AWO or .AWO2 or .AWO3 or :3AWO;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.695
VAL603
4.041
ALA621
3.612
LYS623
3.315
GLU640
2.548
VAL643
4.633
LEU644
3.729
LEU647
4.091
ILE653
3.487
VAL654
4.035
THR670
3.222
GLU671
3.420
TYR672
3.291
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 6-(4-ethylpiperazin-1-yl)-2-methyl-N-(5-(pyridin-4-yl)thiazol-2-yl)pyrimidin-4-amine | Ligand Info | |||||
| Structure Description | Crystal structure of human c-KIT kinase domain in complex with compound 15a | PDB:6KLA | ||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [8] |
| PDB Sequence |
EVQWKVVEEI
563 NGNNYVYIDP573 TQLPYDHKWE583 FPRNRLSFGK593 TLGAGAFGKV603 VEATAYGLIK 613 SDAAMTVAVK623 MLKPSAHLTE633 REALMSELKV643 LSYLGNHMNI653 VNLLGACTIG 663 GPTLVITEYC673 CYGDLLNFLR683 RKRDSEDDEL762 ALDLEDLLSF772 SYQVAKGMAF 782 LASKNCIHRD792 LAARNILLTH802 GRITKICDFG812 LARDIKNDSN822 YVVKGNARLP 832 VKWMAPESIF842 NCVYTFESDV852 WSYGIFLWEL862 FSLGSSPYPG872 MPVDSKFYKM 882 IKEGFRMLSP892 EHAPAEMYDI902 MKTCWDADPL912 KRPTFKQIVQ922 LIEKQISES |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .DJX or .DJX2 or .DJX3 or :3DJX;style chemicals stick;color identity;select .A:593 or .A:595 or .A:603 or .A:621 or .A:623 or .A:640 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:799 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-[4-[[5-fluoro-7-(2-methoxyethoxy)-4-quinazolinyl]amino]phenyl]-4-(1-methylethyl)-1H-1,2,3-triazole-1-acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of human c-KIT kinase domain in complex with a small molecule inhibitor, AZD3229 | PDB:6GQM | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [9] |
| PDB Sequence |
SYIDPTQLPY
578 DHKWEFPRNR588 LSFGKTLGAG598 AFGKVVEATA608 QGLIKSDAAM618 TVAVKMLKPS 628 AHSTEREALM638 SELKVLSYLG648 NHENIVNLLG658 ACTHGGPTLV668 ITEYCCYGDL 678 LNFLRRKRDE688 FVPYLYKDFL764 TLEHLLSFSY774 QVAKGMAFLA784 SKNCIHRDLA 794 ARNILLTHGN804 ITKICDFGLA814 RDIKNDSNYV824 DKGNARLPVK834 WMAPESIFNS 844 VYTFESDVWS854 YGIFLWELFS864 LGSSPYPGMP874 VDSKFYKMIK884 EGFRMSSPEY 894 APAEMYDIMK904 TCWDADPDKR914 PTFKQIVQDI924 EKQISES
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F8H or .F8H2 or .F8H3 or :3F8H;style chemicals stick;color identity;select .A:595 or .A:596 or .A:603 or .A:621 or .A:623 or .A:640 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:684 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.576
GLY596
4.793
VAL603
3.548
ALA621
3.516
LYS623
3.491
GLU640
3.565
LEU644
3.601
LEU647
3.583
ILE653
3.492
VAL654
3.277
THR670
3.493
GLU671
3.279
TYR672
3.397
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|||||
| Ligand Name: N-[4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-2-(4-propan-2-yltriazol-1-yl)acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of human c-KIT kinase domain in complex with AZD3229-analogue (compound 35) | PDB:6GQL | ||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | Yes | [9] |
| PDB Sequence |
YSYIDPTQLP
577 YDHKWEFPRN587 RLSFGKTLGA597 GAFGKVVEAT607 AQGLIKSDAA617 MTVAVKMLKP 627 SAHSTEREAL637 MSELKVLSYL647 GNHENIVNLL657 GACTHGGPTL667 VITEYCCYGD 677 LLNFLRRKRD687 EFVPYLYKDF763 LTLEHLLSFS773 YQVAKGMAFL783 ASKNCIHRDL 793 AARNILLTHG803 NITKICDFGL813 ARDIKNDSNY823 VDKGNARLPV833 KWMAPESIFN 843 SVYTFESDVW853 SYGIFLWELF863 SLGSSPYPGM873 PVDSKFYKMI883 KEGFRMSSPE 893 YAPAEMYDIM903 KTCWDADPDK913 RPTFKQIVQD923 IEKQISES
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F8B or .F8B2 or .F8B3 or :3F8B;style chemicals stick;color identity;select .A:595 or .A:596 or .A:603 or .A:621 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU595
3.360
GLY596
4.895
VAL603
3.511
ALA621
3.615
LYS623
3.707
GLU640
3.563
VAL643
4.613
LEU644
3.766
LEU647
3.610
ILE653
3.952
VAL654
3.517
THR670
3.553
GLU671
3.329
|
|||||
| Ligand Name: N-(4,4-dimethyl-2-propyl-3,1-benzoxazin-6-yl)-2-[3-methoxy-5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of the kinase domain of human c-KIT with a cyclic imidate inhibitor covalently bound to Cys788 | PDB:6XVB | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [10] |
| PDB Sequence |
SYIDPTQLPY
578 DHKWEFPRNR588 LSFGKTLGAG598 AFGKVVEATA608 QGLIKSDAAM618 TVAVKMLKPS 628 AHSTEREALM638 SELKVLSYLG648 NHENIVNLLG658 ACTHGGPTLV668 ITEYCCYGDL 678 LNFLRRKRDE688 FVPYLYKDFL764 TLEHLLSFSY774 QVAKGMAFLA784 SKNCIHRDLA 794 ARNILLTHGN804 ITKICDFGLA814 RDIKNDSNYV824 DKGNARLPVK834 WMAPESIFNS 844 VYTFESDVWS854 YGIFLWELFS864 LGSSPYPGMP874 VDSKFYKMIK884 EGFRMSSPEY 894 APAEMYDIMK904 TCWDADPDKR914 PTFKQIVQDI924 EKQISES
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .O2H or .O2H2 or .O2H3 or :3O2H;style chemicals stick;color identity;select .A:571 or .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:669 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:783 or .A:788 or .A:789 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE571
4.885
LEU595
3.642
VAL603
3.638
ALA621
3.400
VAL622
3.934
LYS623
3.463
GLU640
2.756
VAL643
3.976
LEU644
3.725
LEU647
3.648
ILE653
3.544
VAL654
3.495
VAL668
3.435
ILE669
4.865
THR670
3.282
|
|||||
| Ligand Name: N-[[3-[[2-[3-methoxy-5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]acetyl]amino]-5-methylphenyl]methyl]propanamide | Ligand Info | |||||
| Structure Description | Crystal structure of the kinase domain of human c-KIT in complex with a type-II inhibitor bearing an acrylamide | PDB:6XVA | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [10] |
| PDB Sequence |
SYIDPTQLPY
578 DHKWEFPRNR588 LSFGKTLGAG598 AFGKVVEATA608 QGLIKSDAAM618 TVAVKMLKPS 628 AHSTEREALM638 SELKVLSYLG648 NHENIVNLLG658 ACTHGGPTLV668 ITEYCCYGDL 678 LNFLRRKRDE688 FVPYDFLTLE767 HLLSFSYQVA777 KGMAFLASKN787 CIHRDLAARN 797 ILLTHGNITK807 ICDFGLARDI817 KNDSNYVDKG827 NARLPVKWMA837 PESIFNSVYT 847 FESDVWSYGI857 FLWELFSLGS867 SPYPGMPVDS877 KFYKMIKEGF887 RMSSPEYAPA 897 EMYDIMKTCW907 DADPDKRPTF917 KQIVQDIEKQ927 ISES
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .O2K or .O2K2 or .O2K3 or :3O2K;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:636 or .A:639 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:669 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU595
3.611
VAL603
3.534
ALA621
3.343
VAL622
4.055
LYS623
3.481
ALA636
4.594
SER639
4.242
GLU640
2.879
VAL643
3.852
LEU644
3.757
LEU647
4.476
ILE653
3.806
VAL654
2.868
VAL668
3.483
ILE669
4.905
|
|||||
| Ligand Name: N-[4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-2-(1-ethylpyrazol-4-yl)acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of human c-KIT kinase domain in complex with AZD3229-analogue (compound 23) | PDB:6GQK | ||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | Yes | [9] |
| PDB Sequence |
NYSYIDPTQL
576 PYDHKWEFPR586 NRLSFGKTLG596 AGAFGKVVEA606 TAQGLIKSDA616 AMTVAVKMLK 626 PSAHSTEREA636 LMSELKVLSY646 LGNHENIVNL656 LGACTHGGPT666 LVITEYCCYG 676 DLLNFLRRKR686 DEFVPYKVAP696 EDLYKDFLTL766 EHLLSFSYQV776 AKGMAFLASK 786 NCIHRDLAAR796 NILLTHGNIT806 KICDFGLARD816 IKNDSNYVDK826 GNARLPVKWM 836 APESIFNSVY846 TFESDVWSYG856 IFLWELFSLG866 SSPYPGMPVD876 SKFYKMIKEG 886 FRMSSPEYAP896 AEMYDIMKTC906 WDADPDKRPT916 FKQIVQDIEK926 QISES |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F88 or .F882 or .F883 or :3F88;style chemicals stick;color identity;select .A:595 or .A:596 or .A:603 or .A:621 or .A:623 or .A:640 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU595
3.293
GLY596
4.753
VAL603
3.391
ALA621
3.560
LYS623
3.301
GLU640
3.765
LEU644
3.465
LEU647
4.331
ILE653
3.781
VAL654
4.188
THR670
3.654
GLU671
3.326
|
|||||
| Ligand Name: N-[3-[(dimethylamino)methyl]-5-methylphenyl]-2-[3-methoxy-5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of the kinase domain of human c-KIT in complex with a type-II inhibitor | PDB:6XV9 | ||||
| Method | X-ray diffraction | Resolution | 3.38 Å | Mutation | Yes | [10] |
| PDB Sequence |
NNYSYIDPTQ
575 LPYDHKWEFP585 RNRLSFGKTL595 GAGAFGKVVE605 ATAQGLIKSD615 AAMTVAVKML 625 KPSAHSTERE635 ALMSELKVLS645 YLGNHENIVN655 LLGACTHGGP665 TLVITEYCCY 675 GDLLNFLRRK685 RDEFVPYKVA695 PEDLYKDFLT765 LEHLLSFSYQ775 VAKGMAFLAS 785 KNCIHRDLAA795 RNILLTHGNI805 TKICDFGLAR815 DIKNDSNYVD825 KGNARLPVKW 835 MAPESIFNSV845 YTFESDVWSY855 GIFLWELFSL865 GSSPYPGMPV875 DSKFYKMIKE 885 GFRMSSPEYA895 PAEMYDIMKT905 CWDADPDKRP915 TFKQIVQDIE925 KQISES |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .O35 or .O352 or .O353 or :3O35;style chemicals stick;color identity;select .A:568 or .A:595 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:669 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:783 or .A:788 or .A:789 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR568
4.175
LEU595
3.657
VAL603
3.557
ALA621
3.288
VAL622
3.910
LYS623
3.330
GLU640
3.047
VAL643
3.826
LEU644
3.699
LEU647
4.158
ILE653
3.515
VAL654
4.227
VAL668
3.279
ILE669
4.830
THR670
3.388
GLU671
2.920
|
|||||
| Ligand Name: 2-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-2-methoxy-phenyl]-~{N}-(1-propan-2-ylpyrazol-4-yl)ethanamide | Ligand Info | |||||
| Structure Description | Crystal structure of human c-KIT kinase domain in complex with AZD3229-analogue (compound 18) | PDB:6GQJ | ||||
| Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | Yes | [9] |
| PDB Sequence |
NYSYIDPTQL
576 PYDHKWEFPR586 NRLSFGKTLG596 AGAFGKVVEA606 TAQGLIKSDA616 AMTVAVKMLK 626 PSAHSTEREA636 LMSELKVLSY646 LGNHENIVNL656 LGACTHGGPT666 LVITEYCCYG 676 DLLNFLRRKR686 DEFVPYKKDF763 LTLEHLLSFS773 YQVAKGMAFL783 ASKNCIHRDL 793 AARNILLTHG803 NITKICDFGL813 ARDIKNDSNY823 VDKGNARLPV833 KWMAPESIFN 843 SVYTFESDVW853 SYGIFLWELF863 SLGSSPYPGM873 PVDSKFYKMI883 KEGFRMSSPE 893 YAPAEMYDIM903 KTCWDADPDK913 RPTFKQIVQD923 IEKQISES
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F82 or .F822 or .F823 or :3F82;style chemicals stick;color identity;select .A:595 or .A:596 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:669 or .A:670 or .A:671 or .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:677 or .A:783 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU595
3.424
GLY596
4.513
VAL603
3.419
ALA621
3.384
VAL622
3.914
LYS623
3.383
GLU640
2.728
VAL643
4.924
LEU644
3.628
LEU647
3.698
ILE653
3.394
VAL654
4.596
VAL668
3.449
ILE669
4.778
THR670
3.294
|
|||||
| Ligand Name: N-{4-chloro-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl}-N'-phenylurea | Ligand Info | |||||
| Structure Description | Crystal structure of KIT1 in complex with DP2976 via co-crystallization | PDB:6MOB | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [11] |
| PDB Sequence |
NYVYIDPTQL
576 PYDHKWEFPR586 NRLSFGKTLG596 AGAFGKVVEA606 TAYGLIKSDA616 AMTVAVKMLK 626 PSAHLTEREA636 LMSELKVLSY646 LGNHMNIVNL656 LGACTIGGPT666 LVITEYCCYG 676 DLLNFLRRKR686 DSFICSKTSP754 AIMEDDELAL764 DLEDLLSFSY774 QVAKGMAFLA 784 SKNCIHRDLA794 ARNILLTHGR804 ITKICDFGLA814 RDIKNDSNYV824 VKGNARLPVK 834 WMAPESIFNC844 VYTFESDVWS854 YGIFLWELFS864 LGSSPYPGMP874 VDSKFYKMIK 884 EGFRMLSPEH894 APAEMYDIMK904 TCWDADPLKR914 PTFKQIVQLI924 EKQISE |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JWY or .JWY2 or .JWY3 or :3JWY;style chemicals stick;color identity;select .A:595 or .A:596 or .A:603 or .A:621 or .A:622 or .A:623 or .A:640 or .A:641 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:668 or .A:670 or .A:671 or .A:672 or .A:673 or .A:676 or .A:783 or .A:788 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811 or .A:814; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU595
4.003
GLY596
4.151
VAL603
3.626
ALA621
3.433
VAL622
3.870
LYS623
3.108
GLU640
3.118
LEU641
4.652
VAL643
4.124
LEU644
3.531
LEU647
3.760
ILE653
4.216
VAL654
3.570
VAL668
3.465
|
|||||
| Ligand Name: N-(2,3-dimethylphenyl)-5-(4-pyridin-4-yloxyphenyl)-1H-1,2,4-triazol-3-amine | Ligand Info | |||||
| Structure Description | Structure of c-Kit with allosteric inhibitor 3G8 | PDB:6HH1 | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [12] |
| PDB Sequence |
GNNYVYIDPT
574 QLPYDHKWEF584 PRNRLSFGKT594 LGAGAFGKVV604 EATAYGLIKS614 DAAMTVAVKM 624 LKPSAHLTER634 EALMSELKVL644 SYLGNHMNIV654 NLLGACTIGG664 PTLVITEYCC 674 YGDLLNFLRR684 KRDSFICSKT694 SPAIELALDL766 EDLLSFSYQV776 AKGMAFLASK 786 NCIHRDLAAR796 NILLTHGRIT806 KICDFGLARD816 IKNDSNYVVK826 GNARLPVKWM 836 APESIFNCVY846 TFESDVWSYG856 IFLWELFSLG866 SSPYPGMPVD876 SKFYKMIKEG 886 FRMLSPEHAP896 AEMYDIMKTC906 WDADPLKRPT916 FKQIVQLIEK926 QIS |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .G4E or .G4E2 or .G4E3 or :3G4E;style chemicals stick;color identity;select .A:595 or .A:603 or .A:621 or .A:623 or .A:640 or .A:643 or .A:644 or .A:647 or .A:653 or .A:654 or .A:670 or .A:671 or .A:672 or .A:673 or .A:783 or .A:788 or .A:789 or .A:790 or .A:799 or .A:808 or .A:809 or .A:810 or .A:811; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU595
3.661
VAL603
3.535
ALA621
3.722
LYS623
2.595
GLU640
3.837
VAL643
3.925
LEU644
3.254
LEU647
4.024
ILE653
4.389
VAL654
3.820
THR670
3.836
GLU671
3.125
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1542-7. | ||||
| REF 2 | Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1343-1350. | ||||
| REF 3 | Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014 Nov 15;20(22):5745-5755. | ||||
| REF 4 | Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004 Jul 23;279(30):31655-63. | ||||
| REF 5 | Crystal structure of activated c-KIT in complex with compound | ||||
| REF 6 | Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem. 2003 Aug 22;278(34):31461-4. | ||||
| REF 7 | Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5689-94. | ||||
| REF 8 | Identification of a Multitargeted Tyrosine Kinase Inhibitor for the Treatment of Gastrointestinal Stromal Tumors and Acute Myeloid Leukemia. J Med Chem. 2019 Dec 26;62(24):11135-11150. | ||||
| REF 9 | Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy)quinazolin-4-yl]amino}phenyl)-2-[4-(propan-2-yl)-1 H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT Mutant Inhibitor for the Treatment of Gastrointestinal Stromal Tumors. J Med Chem. 2018 Oct 11;61(19):8797-8810. | ||||
| REF 10 | Alkynyl Benzoxazines and Dihydroquinazolines as Cysteine Targeting Covalent Warheads and Their Application in Identification of Selective Irreversible Kinase Inhibitors. J Am Chem Soc. 2020 Jun 10;142(23):10358-10372. | ||||
| REF 11 | Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell. 2019 May 13;35(5):738-751.e9. | ||||
| REF 12 | Structure of c-Kit with allosteric inhibitor 3G8 | ||||
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