Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T01092 | Target Info | |||
| Target Name | HUMAN receptor-interacting protein 1 (RIPK1) | ||||
| Synonyms | Receptor-interacting serine/threonine-protein kinase 1; RIP1; RIP-1; RIP; Cell death protein RIP | ||||
| Gene Name | RIPK1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: GSK2982772 | Ligand Info | |||||
| Structure Description | Rip1 Kinase ( flag 1-294, C34A, C127A, C233A, C240A) with GSK772 | PDB:5TX5 | ||||
| Method | X-ray diffraction | Resolution | 2.56 Å | Mutation | Yes | [1] |
| PDB Sequence |
IKMKSSDFLE
19 SAELDSGGKV31 SLAFHRTQGL41 MIMKTVYKGP51 NCIEHNEALL61 EEAKMMNRLR 71 HSRVVKLLGV81 IIEEGKYSLV91 MEYMEKGNLM101 HVLKAEMSTP111 LSVKGRIILE 121 IIEGMAYLHG131 KGVIHKDLKP141 ENILVDNDFH151 IKIADLGLAS161 FKMWSKLNGT 189 LYYMAPEHLN199 DVNAKPTEKS209 DVYSFAVVLW219 AIFANKEPYQ235 QLIMAIKSGN 245 RPDVDDITEY255 CPREIISLMK265 LCWEANPEAR275 PTFPGIEEKF285 RPFYLSQLE |
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|
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GLY29
5.000
VAL31
3.698
ILE43
3.761
MET44
4.110
LYS45
3.646
MET67
3.632
LEU70
3.893
VAL75
3.738
VAL76
3.106
LYS77
4.551
LEU78
3.514
LEU90
3.476
|
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| Ligand Name: GSK3145095 | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with GSK3145095 | PDB:6RLN | ||||
| Method | X-ray diffraction | Resolution | 2.87 Å | Mutation | Yes | [2] |
| PDB Sequence |
NVIKMKSSDF
17 LEKVSLAFHR37 TQGLMIMKTV47 YKGPNCIEHN57 EALLEEAKMM67 NRLRHSRVVK 77 LLGVIIEEGK87 YSLVMEYMEK97 GNLMHVLKAE107 MSTPLSVKGR117 IILEIIEGMA 127 YLHGKGVIHK137 DLKPENILVD147 NDFHIKIADL157 GLASFKMWSK167 LNNEEHNELG 188 TLYYMAPEHL198 NDVNAKPTEK208 SDVYSFAVVL218 WAIFANKEPY228 ENAIAEQQLI 238 MAIKSGNRPD248 VDDITEYCPR258 EIISLMKLCW268 EANPEARPTF278 PGIEEKFRPF 288 YLSQLE
|
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VAL31
3.404
ILE43
3.458
MET44
3.386
LYS45
3.355
MET67
4.277
LEU70
3.648
VAL75
3.642
VAL76
3.358
LYS77
4.733
LEU78
3.419
LEU90
3.042
VAL91
3.970
|
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| Ligand Name: GNE684 | Ligand Info | |||||
| Structure Description | Structure of human RIPK1 kinase domain in complex with GNE684 | PDB:6NYH | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [3] |
| PDB Sequence |
NVIKMKSSDF
17 LEKVSLAFHR37 TQGLMIMKTV47 YKGPNCIEHN57 EALLEEAKMM67 NRLRHSRVVK 77 LLGVIIEEGK87 YSLVMEYMEK97 GNLMHVLKAE107 MSTPLSVKGR117 IILEIIEGMA 127 YLHGKGVIHK137 DLKPENILVD147 NDFHIKIADL157 GLASFKMWSK167 LNNEEHNEGT 189 LYYMAPEHLN199 DVNAKPTEKS209 DVYSFAVVLW219 AIFANKEPYE229 NAIAEQQLIM 239 AIKSGNRPDV249 DDITEYCPRE259 IISLMKLCWE269 ANPEARPTFP279 GIEEKFRPFY 289 LSQLE
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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 .L8D or .L8D2 or .L8D3 or :3L8D;style chemicals stick;color identity;select .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:68 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL31
3.838
ILE43
3.474
MET44
3.939
LYS45
3.404
MET67
3.330
ASN68
4.690
LEU70
3.899
VAL75
3.582
VAL76
3.285
LYS77
4.585
LEU78
3.413
LEU90
3.259
|
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| Ligand Name: 1-[4-(1-Aminoisoquinolin-5-Yl)phenyl]-3-(5-Tert-Butyl-1,2-Oxazol-3-Yl)urea | Ligand Info | |||||
| Structure Description | X-ray structure of Receptor Interacting Protein 1 (RIP1)kinase domain with a 1-aminoisoquinoline inhibitor | PDB:4NEU | ||||
| Method | X-ray diffraction | Resolution | 2.57 Å | Mutation | No | [4] |
| PDB Sequence |
SLNVIKMKSS
15 DFLESAELDS25 GGFGKVSLCF35 HRTQGLMIMK45 TVYKGPNCIE55 HNEALLEEAK 65 MMNRLRHSRV75 VKLLGVIIEE85 GKYSLVMEYM95 EKGNLMHVLK105 AEMSTPLSVK 115 GRIILEIIEG125 MCYLHGKGVI135 HKDLKPENIL145 VDNDFHIKIA155 DLGLASFKMW 165 GTLYYMAPEH197 LNDVNAKPTE207 KSDVYSFAVV217 LWAIFANKEP227 YENAICEQQL 237 IMCIKSGNRP247 DVDDITEYCP257 REIISLMKLC267 WEANPEARPT277 FPGIEEKFRP 287 FYLSQLEESV297 EEDVKSLKKE307 YSNENA
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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 .Q1A or .Q1A2 or .Q1A3 or :3Q1A;style chemicals stick;color identity;select .A:23 or .A:31 or .A:43 or .A:45 or .A:63 or .A:66 or .A:67 or .A:70 or .A:75 or .A:76 or .A:92 or .A:93 or .A:94 or .A:95 or .A:98 or .A:129 or .A:134 or .A:136 or .A:145 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU23
3.953
VAL31
3.791
ILE43
3.653
LYS45
4.277
GLU63
2.864
MET66
3.802
MET67
3.593
LEU70
3.303
VAL75
3.778
VAL76
3.431
MET92
3.692
GLU93
3.405
|
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| Ligand Name: (5R)-5-methyl-N-[(3S)-5-methyl-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-4,5,6,7-tetrahydro-2H-indazole-3-carboxamide | Ligand Info | |||||
| Structure Description | Structure of human RIPK1 kinase domain in complex with compound 11 | PDB:6NW2 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [5] |
| PDB Sequence |
NVIKMKSSDF
17 LKVSLAFHRT38 QGLMIMKTVY48 KGPNCIEHNE58 ALLEEAKMMN68 RLRHSRVVKL 78 LGVIIEEGKY88 SLVMEYMEKG98 NLMHVLKAEM108 STPLSVKGRI118 ILEIIEGMAY 128 LHGKGVIHKD138 LKPENILVDN148 DFHIKIADLG158 LASFKMWSKL168 NNEEHNELTL 190 YYMAPEHLAK204 PTEKSDVYSF214 AVVLWAIFAN224 KEPYENAIAE234 QQLIMAIKSG 244 NRPDVDDITE254 YCPREIISLM264 KLCWEANPEA274 RPTFPGIEEK284 FRPFYLSQLE 294
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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 .L4Y or .L4Y2 or .L4Y3 or :3L4Y;style chemicals stick;color identity;select .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL31
3.859
ILE43
3.516
MET44
4.429
LYS45
3.430
MET67
3.495
LEU70
3.852
VAL75
3.599
VAL76
3.339
LYS77
4.518
LEU78
3.198
LEU90
3.152
|
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| Ligand Name: 5-Benzyl-N-[(3s)-5-Methyl-4-Oxo-2,3,4,5-Tetrahydro-1,5-Benzoxazepin-3-Yl]-1,2-Oxazole-3-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase with a benzo[b][1,4]oxazepin-4-one | PDB:5HX6 | ||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | Yes | [6] |
| PDB Sequence |
IKMKSSDFLE
19 SAELDSGKVS32 LAFHRTQGLM42 IMKTVYKGPN52 CIEHNEALLE62 EAKMMNRLRH 72 SRVVKLLGVI82 IEEGKYSLVM92 EYMEKGNLMH102 VLKAEMSTPL112 SVKGRIILEI 122 IEGMAYLHGK132 GVIHKDLKPE142 NILVDNDFHI152 KIADLGLASF162 KMWSKLNGTL 190 YYMAPEHLND200 VNAKPTEKSD210 VYSFAVVLWA220 IFANKEPYEQ235 QLIMAIKSGN 245 RPDVDDITEY255 CPREIISLMK265 LCWEANPEAR275 PTFPGIEEKF285 RPFYLSQLE |
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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 .65U or .65U2 or .65U3 or :365U;style chemicals stick;color identity;select .A:29 or .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:161 or .A:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLY29
4.404
VAL31
2.213
ILE43
2.358
MET44
3.232
LYS45
2.392
MET67
2.844
LEU70
2.368
VAL75
2.508
VAL76
2.572
LYS77
4.251
LEU78
2.428
LEU90
2.337
VAL91
2.964
|
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| Ligand Name: 1-[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]-2,2-dimethylpropan-1-one | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with a pyrrolidine | PDB:6OCQ | ||||
| Method | X-ray diffraction | Resolution | 2.79 Å | Mutation | Yes | [7] |
| PDB Sequence |
NVIKMKSSDF
17 LESAEGKVSL33 AFHRTQGLMI43 MKTVYKGPNC53 IEHNEALLEE63 AKMMNRLRHS 73 RVVKLLGVII83 EEGKYSLVME93 YMEKGNLMHV103 LKAEMSTPLS113 VKGRIILEII 123 EGMAYLHGKG133 VIHKDLKPEN143 ILVDNDFHIK153 IADLGLASFK163 MWSKLNTLYY 192 MAPEHLNDVN202 AKPTEKSDVY212 SFAVVLWAIF222 ANKEPYENAI232 AEQQLIMAIK 242 SGNRPDVDDI252 TEYCPREIIS262 LMKLCWEANP272 EARPTFPGIE282 EKFRPFYLSQ 292 LE
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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 .M5J or .M5J2 or .M5J3 or :3M5J;style chemicals stick;color identity;select .A:67 or .A:70 or .A:75 or .A:76 or .A:78 or .A:90 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: [(5~{S})-5-[3,5-bis(fluoranyl)phenyl]pyrazolidin-1-yl]-[1-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-4-yl]methanone | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with DHP77 | PDB:6R5F | ||||
| Method | X-ray diffraction | Resolution | 3.25 Å | Mutation | Yes | [7] |
| PDB Sequence |
VIKMKSSDSL
33 AFHRTQGLMI43 MKTGPNCIEH56 NEALLEEAKM66 MNRLRHSRVV76 KLLGVIIEEG 86 KYSLVMEYME96 KGNLMHVLKA106 EMSTPLSVKG116 RIILEIIEGM126 AYLHGKGVIH 136 KDLKPENILV146 DNDFHIKIAD156 LGLASFKMWS166 KLNNEETLYY192 MAPEHLNDVN 202 AKPTEKSDVY212 SFAVVLWAIF222 ANKEPYENAI232 AEQQLIMAIK242 SGNRPDVDDI 252 TEYCPREIIS262 LMKLCWEANP272 EARPTFPGIE282 EKFRPFYLSQ292 LE |
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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 .JSW or .JSW2 or .JSW3 or :3JSW;style chemicals stick;color identity;select .A:43 or .A:44 or .A:45 or .A:67 or .A:68 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE43
3.341
MET44
3.569
LYS45
3.420
MET67
3.046
ASN68
4.648
LEU70
3.647
VAL75
3.860
VAL76
3.159
LYS77
4.816
LEU78
3.544
LEU90
4.335
VAL91
4.836
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| Ligand Name: 6-[4-[(5~{S})-5-[3,5-bis(fluoranyl)phenyl]pyrazolidin-1-yl]carbonylpiperidin-1-yl]pyrimidine-4-carbonitrile | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with GSK547 | PDB:6HHO | ||||
| Method | X-ray diffraction | Resolution | 3.49 Å | Mutation | Yes | [8] |
| PDB Sequence |
NVIKMKSSDF
17 LESAELDFGK30 VSLAFHRTQG40 LMIMKTVYKG50 PNCIEHNEAL60 LEEAKMMNRL 70 RHSRVVKLLG80 VIIEEGKYSL90 VMEYMEKGNL100 MHVLKAEMST110 PLSVKGRIIL 120 EIIEGMAYLH130 GKGVIHKDLK140 PENILVDNDF150 HIKIADLGLA160 SFKMWSKLNN 170 EEHNELGTLY191 YMAPEHLNDV201 NAKPTEKSDV211 YSFAVVLWAI221 FANKEPYENA 231 IAEQQLIMAI241 KSGNRPDVDD251 ITEYCPREII261 SLMKLCWEAN271 PEARPTFPGI 281 EEKFRPFYLS291 QLE
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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 .G4W or .G4W2 or .G4W3 or :3G4W;style chemicals stick;color identity;select .A:28 or .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:68 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE28
4.809
VAL31
3.302
ILE43
3.655
MET44
4.061
LYS45
3.243
MET67
3.093
ASN68
4.795
LEU70
3.563
VAL75
3.868
VAL76
3.218
LYS77
4.682
LEU78
3.305
LEU90
3.524
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| Ligand Name: N-[(3S)-5-methyl-7-[2-(oxan-4-yl)ethynyl]-4-oxidanylidene-2,3-dihydro-1,5-benzoxazepin-3-yl]-5-(phenylmethyl)-4H-1,2,4-triazole-3-carboxamide | Ligand Info | |||||
| Structure Description | Crystal Structure of human RIPK1 kinase domain in complex with a novel inhibitor | PDB:7FD0 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [9] |
| PDB Sequence |
VIKMKSSDFL
18 ESAELDSGGF28 GKVSLAFHRT38 QGLMIMKTVY48 KGPNCIEHNE58 ALLEEAKMMN 68 RLRHSRVVKL78 LGVIIEEGKY88 SLVMEYMEKG98 NLMHVLKAEM108 STPLSVKGRI 118 ILEIIEGMAY128 LHGKGVIHKD138 LKPENILVDN148 DFHIKIADLG158 LASFKMWSKL 168 NLYYMAPEHL198 NDVNAKPTEK208 SDVYSFAVVL218 WAIFANKEPY228 ENAIAEQQLI 238 MAIKSGNRPD248 VDDITEYCPR258 EIISLMKLCW268 EANPEARPTF278 PGIEEKFRPF 288 YLSQLE
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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 .3IU or .3IU2 or .3IU3 or :33IU;style chemicals stick;color identity;select .A:23 or .A:24 or .A:25 or .A:28 or .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:95 or .A:98 or .A:99 or .A:129 or .A:134 or .A:136 or .A:145 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU23
4.369
ASP24
3.574
SER25
3.610
PHE28
4.164
VAL31
3.733
ILE43
3.374
MET44
4.218
LYS45
3.700
MET67
3.376
LEU70
3.670
VAL75
3.729
VAL76
3.113
LYS77
4.509
LEU78
3.218
LEU90
3.450
VAL91
3.968
|
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| Ligand Name: N-[(3S)-7-(2-cyclopropylethynyl)-5-methyl-4-oxidanylidene-2,3-dihydro-1,5-benzoxazepin-3-yl]-5-(phenylmethyl)-4H-1,2,4-triazole-3-carboxamide | Ligand Info | |||||
| Structure Description | Crystal Structure of human RIPK1 kinase domain in complex with a novel inhibitor | PDB:7FCZ | ||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | Yes | [9] |
| PDB Sequence |
IKMKSSDFLE
19 SAELDKVSLA34 FHRTQGLMIM44 KTVYKGNEAL60 LEEAKMMNRL70 RHSRVVKLLG 80 VIIEEGKYSL90 VMEYMEKGNL100 MHVLKASTPL112 SVKGRIILEI122 IEGMAYLHGK 132 GVIHKDLKPE142 NILVDNDFHI152 KIADLGLASF162 KMWSKLNGTL190 YYMAPEHLND 200 VNAKPTEKSD210 VYSFAVVLWA220 IFANKEPYQQ236 LIMAIKSGNR246 PDVDDITEYC 256 PREIISLMKL266 CWEANPEARP276 TFPGIEEKFR286 PFYLSQLE
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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 .3IF or .3IF2 or .3IF3 or :33IF;style chemicals stick;color identity;select .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL31
3.914
ILE43
3.626
MET44
4.340
LYS45
3.556
MET67
3.953
LEU70
3.787
VAL75
3.492
VAL76
2.993
LYS77
4.394
LEU78
3.496
LEU90
3.483
VAL91
4.172
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| Ligand Name: RIP1 kinase inhibitor 1 | Ligand Info | |||||
| Structure Description | Structure based design of RIP1 kinase inhibitors | PDB:6C4D | ||||
| Method | X-ray diffraction | Resolution | 2.52 Å | Mutation | No | [10] |
| PDB Sequence |
NVIKMKSSDF
17 LEGFGKVSLA34 FHRTQGLMIM44 KTVYKGPNCI54 EHNEALLEEA64 KMMNRLRHSR 74 VVKLLGVIIE84 EGKYSLVMEY94 MEKGNLMHVL104 KAEMSTPLSV114 KGRIILEIIE 124 GMAYLHGKGV134 IHKDLKPENI144 LVDNDFHIKI154 ADLGLASFKM164 WSKLNNEEHN 174 GTLYYMAPEH197 LNDVNAKPTE207 KSDVYSFAVV217 LWAIFANKEP227 YENAIAEQQL 237 IMAIKSGNRP247 DVDDITEYCP257 REIISLMKLC267 WEANPEARPT277 FPGIEEKFRP 287 FYLSQLE
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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 .EJP or .EJP2 or .EJP3 or :3EJP;style chemicals stick;color identity;select .A:28 or .A:31 or .A:43 or .A:44 or .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE28
3.382
VAL31
4.154
ILE43
3.894
MET44
4.456
LYS45
3.804
MET67
3.489
LEU70
3.579
VAL75
3.672
VAL76
3.142
LYS77
4.505
LEU78
3.749
LEU90
3.436
|
|||||
| Ligand Name: 2-Benzyl-5-nitro-1H-benzimidazole | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF RIP1 KINASE BOUND TO INHIBITOR | PDB:6C3E | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [10] |
| PDB Sequence |
VIKMKSSDFL
18 ESAELDSGGF28 GKVSLAFHRT38 QGLMIMKTVY48 KIEHNEALLE62 EAKMMNRLRH 72 SRVVKLLGVI82 IEEGKYSLVM92 EYMEKGNLMH102 VLKAEMSTPL112 SVKGRIILEI 122 IEGMAYLHGK132 GVIHKDLKPE142 NILVDNDFHI152 KIADLGLASF162 KMWSKLNNGT 189 LYYMAPEHLP205 TEKSDVYSFA215 VVLWAIFANK225 EPYENAIAEQ235 QLIMAIKSGN 245 RPDVDDLTEY255 CPREIISLMK265 LCWEANPEAR275 PTFPGIEEKF285 RPFYLSQL |
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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 .EJY or .EJY2 or .EJY3 or :3EJY;style chemicals stick;color identity;select .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; 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-[(1s)-1-(2-Chloro-6-Fluorophenyl)ethyl]-5-Cyano-1-Methyl-1h-Pyrrole-2-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with necrostatin-4 | PDB:4ITJ | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [11] |
| PDB Sequence |
NVIKMKSSDF
17 LEFGKVSLAF35 HRTQGLMIMK45 TVYKGPNCIE55 HNEALLEEAK65 MMNRLRHSRV 75 VKLLGVIIEE85 GKYSLVMEYM95 EKGNLMHVLK105 AEMSTPLSVK115 GRIILEIIEG 125 MAYLHGKGVI135 HKDLKPENIL145 VDNDFHIKIA155 DLGLASFKMW165 SKLNGTLYYM 193 APEHLNDVNA203 KPTEKSDVYS213 FAVVLWAIFA223 NKEPYENAIA233 EQQLIMAIKS 243 GNRPDVDDIT253 EYCPREIISL263 MKLCWEANPE273 ARPTFPGIEE283 KFRPFYLSQL 293 E
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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 .1HX or .1HX2 or .1HX3 or :31HX;style chemicals stick;color identity;select .A:45 or .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:91 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (5r)-5-[(7-Chloro-1h-Indol-3-Yl)methyl]-3-Methylimidazolidine-2,4-Dione | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with necrostatin-1 analog | PDB:4ITH | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [11] |
| PDB Sequence |
NVIKMKSSDF
17 LVSLAFHRTQ39 GLMIMKTVNE58 ALLEEAKMMN68 RLRHSRVVKL78 LGVIIEEGKY 88 SLVMEYMEKG98 NLMHVLKAEM108 STPLSVKGRI118 ILEIIEGMAY128 LHGKGVIHKD 138 LKPENILVDN148 DFHIKIADLG158 LASFKMWSKL168 GTLYYMAPEH197 LNDVNAKPTE 207 KSDVYSFAVV217 LWAIFANKEP227 YENAIAEQQL237 IMAIKSGNRP247 DVDDITEYCP 257 REIISLMKLC267 WEANPEARPT277 FPGIEEKFRP287 FYLSQLE
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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 .RCM or .RCM2 or .RCM3 or :3RCM;style chemicals stick;color identity;select .A:67 or .A:70 or .A:75 or .A:76 or .A:77 or .A:78 or .A:90 or .A:92 or .A:129 or .A:134 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159 or .A:161 or .A:162; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-((3S,3aS)-3-(3-Fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl)-2-hydroxyethanone | Ligand Info | |||||
| Structure Description | Crystal structure of RIP1 kinase in complex with necrostatin-3 analog | PDB:4ITI | ||||
| Method | X-ray diffraction | Resolution | 2.86 Å | Mutation | Yes | [11] |
| PDB Sequence |
NVIKMKSSDF
17 LESAELDSGG27 FGKVSLAFHR37 TQGLMIMKTV47 YKGPNCIEHN57 EALLEEAKMM 67 NRLRHSRVVK77 LLGVIIEEGK87 YSLVMEYMEK97 GNLMHVLKAE107 MSTPLSVKGR 117 IILEIIEGMA127 YLHGKGVIHK137 DLKPENILVD147 NDFHIKIADL157 GLASFKMWSK 167 LNNEEHNELG187 GTLYYMAPEH197 LNDVNAKPTE207 KSDVYSFAVV217 LWAIFANKEP 227 YEQQLIMAIK242 SGNRPDVDDI252 TEYCPREIIS262 LMKLCWEANP272 EARPTFPGIE 282 EKFRPFYLSQ292 LE
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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 .1HW or .1HW2 or .1HW3 or :31HW;style chemicals stick;color identity;select .A:9 or .A:45 or .A:64 or .A:67 or .A:68 or .A:70 or .A:75 or .A:76 or .A:78 or .A:81 or .A:90 or .A:92 or .A:129 or .A:134 or .A:135 or .A:136 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:161 or .A:162 or .A:165; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL9
4.762
LYS45
3.693
ALA64
3.416
MET67
3.480
ASN68
3.771
LEU70
4.017
VAL75
3.437
VAL76
3.615
LEU78
3.671
VAL81
4.555
LEU90
3.444
MET92
3.692
LEU129
3.829
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261. | ||||
| REF 2 | Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer. ACS Med Chem Lett. 2019 May 9;10(6):857-862. | ||||
| REF 3 | RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases. Cell Death Differ. 2020 Jan;27(1):161-175. | ||||
| REF 4 | Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis. ACS Med Chem Lett. 2013 Nov 4;4(12):1238-43. | ||||
| REF 5 | Potent and selective inhibitors of receptor-interacting protein kinase 1 that lack an aromatic back pocket group. Bioorg Med Chem Lett. 2019 Jun 15;29(12):1497-1501. | ||||
| REF 6 | DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. J Med Chem. 2016 Mar 10;59(5):2163-78. | ||||
| REF 7 | Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase. J Med Chem. 2019 May 23;62(10):5096-5110. | ||||
| REF 8 | RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. Cancer Cell. 2018 Nov 12;34(5):757-774.e7. | ||||
| REF 9 | Potent and Selective RIPK1 Inhibitors Targeting Dual-Pockets for the Treatment of Systemic Inflammatory Response Syndrome and Sepsis. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202114922. | ||||
| REF 10 | Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H-pyrazolo[3,4- c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships. J Med Chem. 2018 Mar 22;61(6):2384-2409. | ||||
| REF 11 | Structural basis of RIP1 inhibition by necrostatins. Structure. 2013 Mar 5;21(3):493-9. | ||||
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