Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T92144 | Target Info | |||
| Target Name | Angiopoietin 1 receptor (TEK) | ||||
| Synonyms | hTIE2; VMCM1; VMCM; Tyrosine-protein kinase receptor TIE-2; Tyrosine-protein kinase receptor TEK; Tyrosine kinase with Ig and EGF homology domains-2; Tunica interna endothelial cell kinase; TIE2; P140 TEK; Endothelial tyrosine kinase; Endothelial Cell-Specific Receptor TIE-2; CD202b antigen; CD202b | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | TEK | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: DCC-2036 | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919 | PDB:6MWE | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [1] |
| PDB Sequence |
YPVLDWNDIK
825 FQDVIGEGNF835 GQVLKARIKK845 DGLRMDAAIK855 RMGELEVLCK878 LGHHPNIINL 888 LGACEHRGYL898 YLAIEYAPHG908 NLLDFLRKSR918 VLETDPAFAI928 ANSTASTLSS 938 QQLLHFAADV948 ARGMDYLSQK958 QFIHRDLAAR968 NILVGENYVA978 KIADFGLSRG 988 QEVYKTMGRL1000 PVRWMAIESL1010 NYSVYTTNSD1020 VWSYGVLLWE1030 IVSLGGTPYC 1040 GMTCAELYEK1050 LPQGYRLEKP1060 LNCDDEVYDL1070 MRQCWREKPY1080 ERPSFAQILV 1090 SLNRMLEERK1100 TYVNTTLYEK1110 FTYAGIDCSA1120 EE
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ILE830
3.616
VAL838
3.778
ALA853
3.433
LYS855
3.139
GLY871
4.636
GLU872
2.750
VAL875
3.651
LEU876
3.692
LEU879
4.151
ILE885
3.518
ILE886
3.508
ILE902
3.779
GLU903
3.158
TYR904
3.852
|
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| Ligand Name: 2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose | Ligand Info | |||||
| Structure Description | Tie2 Ligand-Binding Domain Crystal Structure | PDB:2GY5 | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [2] |
| PDB Sequence |
AMDLILINSL
32 PLVSDAETSL42 TCIASGWRPH52 EPITIGRDFE62 ALMNQHQDPL72 EVTQDVTREW 82 AKKVVWKREK92 ASKINGAYFC102 EGRVRGEAIR112 IRTMKMRQQA122 SFLPATLTMT 132 VDKGDNVNIS142 FKKVLIKEED152 AVIYKNGSFI162 HSVPRHEVPD172 ILEVHLPHAQ 182 PQDAGVYSAR192 YIGGNLFTSA202 FTRLIVRRCE212 AQKWGPECNH222 LCTACMNNGV 232 CHEDTGECIC242 PPGFMGRTCE252 KACELHTFGR262 TCKERCSGQE272 GCKSYVFCLP 282 DPYGCSCATG292 WKGLQCNEAC302 HPGFYGPDCK312 LRCSCNNGEM322 CDRFQGCLCS 332 PGWQGLQCER342 EGIPRMTPKI352 VDLPDHIEVN362 SGKFNPICKA372 SGWPLPTNEE 382 MTLVKPDGTV392 LHPKDFNHTD402 HFSVAIFTIH412 RILPPDSGVW422 VCSVNTVAGM 432 VEKPFNISVK442 VLP
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| Ligand Name: 8-(2,3-Dihydro-1h-Inden-5-Yl)-2-({4-[(3r,5s)-3,5-Dimethylpiperazin-1-Yl]phenyl}amino)-5-Oxo-5,8-Dihydropyrido[2,3-D]pyrimidine-6-Carboxamide | Ligand Info | |||||
| Structure Description | cFMS tyrosine kinase (tie2 KID) in complex with a pyrimidinopyridone inhibitor | PDB:3BEA | ||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | Yes | [3] |
| PDB Sequence |
QVRWKIIESY
556 EGNSYTFIDP566 TQLPYNEKWE576 FPRNNLQFGK586 TLGAGAFGKV596 VEATAFGLGK 606 EDAVLKVAVK616 MLKSTAHADE626 KEALMSELKI636 MSHLGQHENI646 VNLLGACTHG 656 GPVLVITEYC666 CYGDLLNFLR676 RKSRVLSTLS696 TRDLLHFSSQ761 VAQGMAFLAS 771 KNCIHRDVAA781 RNVLLTNGHV791 AKIGDFGLAR801 DIMNDSNYIV811 KGNARLPVKW 821 MAPESIFDCV831 YTVQSDVWSY841 GILLWEIFSL851 GLNPYPGILV861 NSKFYKLVKD 871 GYQMAQPAFA881 PKNIYSIMQA891 CWALEPTHRP901 TFQQICSFLQ911 EQAQEDRRER 921
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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 .IXH or .IXH2 or .IXH3 or :3IXH;style chemicals stick;color identity;select .A:588 or .A:589 or .A:596 or .A:614 or .A:616 or .A:633 or .A:647 or .A:663 or .A:664 or .A:665 or .A:666 or .A:667 or .A:668 or .A:669 or .A:670 or .A:673 or .A:782 or .A:783 or .A:785 or .A:796 or .A:797 or .A:800 or .A:801; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU588
3.511
GLY589
3.642
VAL596
3.942
ALA614
3.510
LYS616
2.682
GLU633
4.619
VAL647
3.073
THR663
2.543
GLU664
3.127
TYR665
3.620
CYS666
2.835
CYS667
4.410
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| Ligand Name: 2-[3-(Cyclohexylmethyl)-5-Phenyl-Imidazol-4-Yl]-[1,3]thiazolo[4,5-E]pyrimidin-7-Amine | Ligand Info | |||||
| Structure Description | Structure of the Tie2 kinase domain in complex with a thiazolopyrimidine inhibitor | PDB:2WQB | ||||
| Method | X-ray diffraction | Resolution | 2.95 Å | Mutation | Yes | [4] |
| PDB Sequence |
YPVLDWNDIK
825 FQDVIGEGGQ837 VLKARIKKDG847 LRMDAAIKRM857 KELEVLCKLG880 HHPNIINLLG 890 ACEHRGYLYL900 AIEYAPHGNL910 LDFLRKSRVL920 ETDPAFAIAN930 STASTLSSQQ 940 LLHFAADVAR950 GMDYLSQKQF960 IHRNLAARNI970 LVGENYVAKI980 ADFGLSRGQE 990 VYVKKTGRLP1001 VRWMAIESLN1011 YSVYTTNSDV1021 WSYGVLLWEI1031 VSLGGTPYCG 1041 MTCAELYEKL1051 PQGYRLEKPL1061 NCDDEVYDLM1071 RQCWREKPYE1081 RPSFAQILVS 1091 LNRMLEERKT1101 YVNTTLYEKF1111 TYAGIDCSA
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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 .QQ1 or .QQ12 or .QQ13 or :3QQ1;style chemicals stick;color identity;select .A:830 or .A:838 or .A:853 or .A:854 or .A:855 or .A:886 or .A:900 or .A:902 or .A:903 or .A:904 or .A:905 or .A:909 or .A:968 or .A:969 or .A:970 or .A:971 or .A:981 or .A:983; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-[4-(4-Amino-5-Oxopyrido[2,3-D]pyrimidin-8(5h)-Yl)phenyl]-3-[2-Fluoro-5-(Trifluoromethyl)phenyl]urea | Ligand Info | |||||
| Structure Description | Selection of fragments for kinase inhibitor design: decoration is key | PDB:4X3J | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [5] |
| PDB Sequence |
VLKARMDAAI
854 KELEVLCKLG880 HHPNIINLLL898 YLAIEYAPHG908 NLLDFLRKSR918 VLETDPAFAI 928 ANSTASTLSS938 QQLLHFAADV948 ARGMDYLSQK958 QFIHRNLAAR968 NILVGENYVA 978 KIADFGLPVR1003 WMAIESLNYS1013 VYTTNSDVWS1023 YGVLLWEIVS1033 LGGTPYCGMT 1043 CAELYEKLPQ1053 GYRLEKPLNC1063 DDEVYDLMRQ1073 CWREKPYERP1083 SFAQILVSLN 1093 RMLEERKTYV1103 NTTLYEKFTY1113 AGID
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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 .3WR or .3WR2 or .3WR3 or :33WR;style chemicals stick;color identity;select .A:838 or .A:853 or .A:855 or .A:872 or .A:875 or .A:876 or .A:879 or .A:885 or .A:886 or .A:902 or .A:903 or .A:904 or .A:905 or .A:908 or .A:909 or .A:955 or .A:960 or .A:962 or .A:971 or .A:980 or .A:981 or .A:982 or .A:983; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL838
4.812
ALA853
3.496
LYS855
3.893
GLU872
2.922
VAL875
3.562
LEU876
3.713
LEU879
3.985
ILE885
3.723
ILE886
3.708
ILE902
3.663
GLU903
3.376
TYR904
3.613
|
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| Ligand Name: N-{3-[3-(Dimethylamino)propyl]-5-(Trifluoromethyl)phenyl}-4-Methyl-3-[(3-Pyrimidin-4-Ylpyridin-2-Yl)amino]benzamide | Ligand Info | |||||
| Structure Description | Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors | PDB:2OO8 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [6] |
| PDB Sequence |
GQVLKARIRM
850 DAAIKRMKEK863 DDHRDFAGEL873 EVLCKLGHHP883 NIINLLGACE893 HYLAIEYAPH 907 GNLLDFLRKS917 RVLETDPAFA927 IANSTASTLS937 SQQLLHFAAD947 VARGMDYLSQ 957 KQFIHRDLAA967 RNILVGENYV977 AKIADFGLMG998 RLPVRWMAIE1008 SLNYSVYTTN 1018 SDVWSYGVLL1028 WEIVSLGGTP1038 YCGMTCAELY1048 EKLPQGYRLE1058 KPLNCDDEVY 1068 DLMRQCWREK1078 PYERPSFAQI1088 LVSLNRMLEE1098 RKTYVNTTLY1108 EKFTYAGID |
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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 .RAJ or .RAJ2 or .RAJ3 or :3RAJ;style chemicals stick;color identity;select .X:838 or .X:853 or .X:854 or .X:855 or .X:872 or .X:875 or .X:876 or .X:879 or .X:886 or .X:900 or .X:902 or .X:903 or .X:904 or .X:905 or .X:955 or .X:960 or .X:962 or .X:971 or .X:980 or .X:981 or .X:982 or .X:983 or .X:984; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL838
3.719
ALA853
3.448
ILE854
4.250
LYS855
3.851
GLU872
2.931
VAL875
4.127
LEU876
3.563
LEU879
3.317
ILE886
3.648
LEU900
4.272
ILE902
3.631
GLU903
3.730
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| Ligand Name: 2-methyl-11-(1-methylethyl)-8-[(2S)-tetrahydro-2H-pyran-2-yl]-2,11,12,13-tetrahydro-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one | Ligand Info | |||||
| Structure Description | Crystal structure of cytoplasmic kinase domain of Tie2 complexed with inhibitor CEP11207 | PDB:3L8P | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [7] |
| PDB Sequence |
TIYPVLDWND
823 IKFQDVIGEG833 NFGQVLKARI843 KKDGLRMDAA853 IKRMFAGELE874 VLCKLGHHPN 884 IINLLGACEH894 RGYLYLAIEY904 APHGNLLDFL914 RKSRVLETDP924 AFAIANSTAS 934 TLSSQQLLHF944 AADVARGMDY954 LSQKQFIHRD964 LAARNILVGE974 NYVAKIADFG 984 LSRGQEVYVK994 KPVRWMAIES1009 LNYSVYTTNS1019 DVWSYGVLLW1029 EIVSLGGTPY 1039 CGMTCAELYE1049 KLPQGYRLEK1059 PLNCDDEVYD1069 LMRQCWREKP1079 YERPSFAQIL 1089 VSLNRMLEER1099 KTYVNTTLYE1109 KFTYAGIDCS1119 AE
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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 .0CE or .0CE2 or .0CE3 or :30CE;style chemicals stick;color identity;select .A:830 or .A:831 or .A:832 or .A:833 or .A:838 or .A:853 or .A:855 or .A:876 or .A:886 or .A:900 or .A:902 or .A:903 or .A:904 or .A:905 or .A:906 or .A:907 or .A:908 or .A:909 or .A:968 or .A:969 or .A:971 or .A:981 or .A:982 or .A:983; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE830
2.970
GLY831
3.676
GLU832
3.459
GLY833
3.801
VAL838
3.597
ALA853
3.339
LYS855
4.434
LEU876
4.159
ILE886
3.839
LEU900
4.170
ILE902
3.454
GLU903
2.823
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| Ligand Name: 4-Methyl-3-({3-[2-(Methylamino)pyrimidin-4-Yl]pyridin-2-Yl}oxy)-N-[2-Morpholin-4-Yl-5-(Trifluoromethyl)phenyl]benzamide | Ligand Info | |||||
| Structure Description | Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor | PDB:2P4I | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [8] |
| PDB Sequence |
VLKARIRMDA
852 AIKRGELEVL876 CKLGHHPNII886 NLLGACEHYL900 AIEYAPHGNL910 LDFLRKSRVL 920 ETDPAFAIAN930 STASTLSSQQ940 LLHFAADVAR950 GMDYLSQKQF960 IHRDLAARNI 970 LVGENYVAKI980 ADFGLSRVKK995 TMGRLPVRWM1005 AIESLNYSVY1015 TTNSDVWSYG 1025 VLLWEIVSLG1035 GTPYCGMTCA1045 ELYEKLPQGY1055 RLEKPLNCDD1065 EVYDLMRQCW 1075 REKPYERPSF1085 AQILVSLNRM1095 LEERKTYVNT1105 TLYEKFTYAG1115 ID |
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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 .MR9 or .MR92 or .MR93 or :3MR9;style chemicals stick;color identity;select .A:838 or .A:853 or .A:854 or .A:855 or .A:872 or .A:875 or .A:876 or .A:879 or .A:885 or .A:886 or .A:900 or .A:902 or .A:903 or .A:904 or .A:905 or .A:908 or .A:955 or .A:960 or .A:962 or .A:971 or .A:980 or .A:981 or .A:982 or .A:983 or .A:984 or .A:985 or .A:986 or .A:987; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL838
3.629
ALA853
3.433
ILE854
4.488
LYS855
3.867
GLU872
3.292
VAL875
4.169
LEU876
3.848
LEU879
3.431
ILE885
4.291
ILE886
3.466
LEU900
4.717
ILE902
3.314
GLU903
3.608
TYR904
3.339
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| Ligand Name: N-{4-Methyl-3-[(3-Pyrimidin-4-Ylpyridin-2-Yl)amino]phenyl}-3-(Trifluoromethyl)benzamide | Ligand Info | |||||
| Structure Description | Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors | PDB:2OSC | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [6] |
| PDB Sequence |
QVLKARIMDA
852 AIKRMKKDDH866 RDFAGELEVL876 CKLGHHPNII886 NLLGACEHYL900 AIEYAPHGNL 910 LDFLRKSRVL920 ETDPAFAIAN930 STASTLSSQQ940 LLHFAADVAR950 GMDYLSQKQF 960 IHRDLAARNI970 LVGENYVAKI980 ADFGLMGRLP1001 VRWMAIESLN1011 YSVYTTNSDV 1021 WSYGVLLWEI1031 VSLGGTPYCG1041 MTCAELYEKL1051 PQGYRLEKPL1061 NCDDEVYDLM 1071 RQCWREKPYE1081 RPSFAQILVS1091 LNRMLEERKT1101 YVNTTLYEKF1111 TYAGI |
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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 .MUH or .MUH2 or .MUH3 or :3MUH;style chemicals stick;color identity;select .A:838 or .A:853 or .A:854 or .A:855 or .A:872 or .A:875 or .A:876 or .A:879 or .A:885 or .A:886 or .A:900 or .A:902 or .A:903 or .A:904 or .A:905 or .A:955 or .A:960 or .A:962 or .A:971 or .A:980 or .A:981 or .A:982 or .A:983; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL838
3.765
ALA853
3.925
ILE854
4.116
LYS855
3.564
GLU872
3.027
VAL875
3.989
LEU876
3.610
LEU879
3.106
ILE885
4.698
ILE886
3.804
LEU900
3.970
ILE902
3.587
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2(Hi) Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors. Mol Cancer Ther. 2017 Nov;16(11):2486-2501. | ||||
| REF 2 | Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex. Nat Struct Mol Biol. 2006 Jun;13(6):524-32. | ||||
| REF 3 | Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2355-61. | ||||
| REF 4 | Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6670-4 | ||||
| REF 5 | Selection of fragments for kinase inhibitor design: decoration is key. J Med Chem. 2015 Jan 8;58(1):457-65. | ||||
| REF 6 | Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. | ||||
| REF 7 | Crystal structure of cytoplasmic kinase domain of Tie2 complexed with inhibitor CEP11207 | ||||
| REF 8 | Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor. J Med Chem. 2007 Feb 22;50(4):611-26. | ||||
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