Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T06093 | Target Info | |||
| Target Name | Rho-associated protein kinase 2 (ROCK2) | ||||
| Synonyms | p164 ROCK-2; Rho-associated, coiled-coil-containing protein kinase II; Rho-associated, coiled-coil-containing protein kinase 2; Rho kinase 2; ROCK-II; KIAA0619 | ||||
| Target Type | Successful Target | ||||
| Gene Name | ROCK2 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: TAK-931 | Ligand Info | |||||
| Structure Description | Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Anti-Tumor Agent | PDB:6P5P | ||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | Yes | [1] |
| PDB Sequence |
QRKLEALIRD
36 PRSPINVESL46 LDGLNSLVLD56 LDFPALRKNK66 NIDNFLNRYE76 KIVKKIRGLQ 86 MKAEDYDVVK96 VIGRGAFGEV106 QLVRHKASQK116 VYAMKLLSKF126 EMIKRSDSAF 136 FWEERDIMAF146 ANSPWVVQLF156 YAFQDDRYLY166 MVMEYMPGGD176 LVNLMSNYDV 186 PEKWAKFYTA196 EVVLALDAIH206 SMGLIHRDVK216 PDNMLLDKHG226 HLKLADFGTC 236 MKMDETGMVH246 CDTAVGTPDY256 ISPEVLKSQG266 GDGYYGRECD276 WWSVGVFLYE 286 MLVGDTPFYA296 DSLVGTYSKI306 MDHKNSLCFP316 EDAEISKHAK326 NLICAFLTDR 336 EVRLGRNGVE346 EIRQHPFFKN356 DQWHWDNIRE366 TAAPVVPELS376 SDIDSSNFDD 386 IEVETFPIPK401 AFVGNQLPFI411 GFTYYR
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| Ligand Name: N-[(2,3-dihydro-1,4-benzodioxin-5-yl)methyl]-4-(pyridin-4-yl)benzamide | Ligand Info | |||||
| Structure Description | Crystal structure of Rock2 with a pyridinylbenzamide based inhibitor | PDB:6ED6 | ||||
| Method | X-ray diffraction | Resolution | 2.86 Å | Mutation | No | [2] |
| PDB Sequence |
QRKLEALIRD
36 PRSPINVESL46 LDGLNSLVLD56 LDFPALRKNK66 NIDNFLNRYE76 KIVKKIRGLQ 86 MKAEDYDVVK96 VIGRGAFGEV106 QLVRHKASQK116 VYAMKLLSKF126 EMIKRSDSAF 136 FWEERDIMAF146 ANSPWVVQLF156 YAFQDDRYLY166 MVMEYMPGGD176 LVNLMSNYDV 186 PEKWAKFYTA196 EVVLALDAIH206 SMGLIHRDVK216 PDNMLLDKHG226 HLKLADFGTC 236 MKMDETGMVH246 CDTAVGTPDY256 ISPEVLKSQF270 YGRECDWWSV280 GVFLYEMLVG 290 DTPFYADSLV300 GTYSKIMDHK310 NSLCFPEDAE320 ISKHAKNLIC330 AFLTDREVRL 340 GRNGVEEIRQ350 HPFFKNDQWH360 WDNIRETAAP370 VVPELSSDID380 SSNFDDIETF 397 PIPKAFVGNQ407 LPFIGFTY
|
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ILE98
3.572
ARG100
4.414
GLY101
3.627
ALA102
3.575
PHE103
3.054
GLY104
3.293
GLU105
3.844
VAL106
3.776
ALA119
3.598
LYS121
2.873
LEU122
3.900
LEU123
3.674
|
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| Ligand Name: 6-(5-methyl-1H-pyrazol-4-yl)-2-(pyrrolidin-1-ylmethyl)thieno[3,2-d]pyrimidin-4(3H)-one | Ligand Info | |||||
| Structure Description | Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Anti-Tumor Agent | PDB:6P5M | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | Yes | [1] |
| PDB Sequence |
SPGDGAGASR
26 QRKLEALIRD36 PRSPINVESL46 LDGLNSLVLD56 LDFPALRKNK66 NIDNFLNRYE 76 KIVKKIRGLQ86 MKAEDYDVVK96 VIGRGAFGEV106 QLVRHKASQK116 VYAMKLLSKF 126 EMIKRSDSAF136 FWEERDIMAF146 ANSPWVVQLF156 YAFQDDRYLY166 MVMEYMPGGD 176 LVNLMSNYDV186 PEKWAKFYTA196 EVVLALDAIH206 SMGLIHRDVK216 PDNMLLDKHG 226 HLKLADFGTC236 MKMDETGMVH246 CDTAVGTPDY256 ISPEVLKSQG266 GDGYYGRECD 276 WWSVGVFLYE286 MLVGDTPFYA296 DSLVGTYSKI306 MDHKNSLCFP316 EDAEISKHAK 326 NLICAFLTDR336 EVRLGRNGVE346 EIRQHPFFKN356 DQWHWDNIRE366 TAAPVVPELS 376 SDIDSSNFDD386 IEVETFPIPK401 AFVGNQLPFI411 GFTYYR
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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 .O1S or .O1S2 or .O1S3 or :3O1S;style chemicals stick;color identity;select .A:98 or .A:106 or .A:119 or .A:121 or .A:140 or .A:144 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:216 or .A:218 or .A:219 or .A:221 or .A:231 or .A:232 or .A:384; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 6-[4-(Aminomethyl)-2-Fluorophenoxy]-2,1-Benzoxaborol-1(3h)-Ol | Ligand Info | |||||
| Structure Description | ROCK2 in complex with benzoxaborole | PDB:4L6Q | ||||
| Method | X-ray diffraction | Resolution | 2.79 Å | Mutation | No | [3] |
| PDB Sequence |
QRKLEALIRD
36 PRSPINVESL46 LDGLNSLVLD56 LDFPALRKNK66 NIDNFLNRYE76 KIVKKIRGLQ 86 MKAEDYDVVK96 VIGRGAFGEV106 QLVRHKASQK116 VYAMKLLSKF126 EMIKRSDSAF 136 FWEERDIMAF146 ANSPWVVQLF156 YAFQDDRYLY166 MVMEYMPGGD176 LVNLMSNYDV 186 PEKWAKFYTA196 EVVLALDAIH206 SMGLIHRDVK216 PDNMLLDKHG226 HLKLADFGTC 236 MKMDETGMVH246 CDTAVGTPDY256 ISPEVLKSQG266 GDGFYGRECD276 WWSVGVFLYE 286 MLVGDTPFYA296 DSLVGTYSKI306 MDHKNSLCFP316 EDAEISKHAK326 NLICAFLTDR 336 EVRLGRNGVE346 EIRQHPFFKN356 DQWHWDNIRE366 TAAPVVPELS376 SDIDSSNFDD 386 IEDDVETFPI399 PKAFVGNQLP409 FIGFTYYR
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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 .1WU or .1WU2 or .1WU3 or :31WU;style chemicals stick;color identity;select .A:98 or .A:106 or .A:119 or .A:121 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:214 or .A:216 or .A:218 or .A:219 or .A:221 or .A:231 or .A:232 or .A:384; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-[(3-methoxyphenyl)methyl]-5H-[1]benzopyrano[3,4-c]pyridine-8-carboxamide | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A POTENT AND SELECTIVE DUAL ROCK INHIBITOR | PDB:7JNT | ||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | No | [4] |
| PDB Sequence |
SRQRKLEALI
34 RDPRSPINVE44 SLLDGLNSLV54 LDLDFPALRK64 NKNIDNFLNR74 YEKIVKKIRG 84 LQMKAEDYDV94 VKVIGRGAFG104 EVQLVRHKAS114 QKVYAMKLLS124 KFEMIKRSDS 134 AFFWEERDIM144 AFANSPWVVQ154 LFYAFQDDRY164 LYMVMEYMPG174 GDLVNLMSNY 184 DVPEKWAKFY194 TAEVVLALDA204 IHSMGLIHRD214 VKPDNMLLDK224 HGHLKLADFG 234 TCMKMDETGM244 VHTPDYISPE260 VLKFYGRECD276 WWSVGVFLYE286 MLVGDTPFYA 296 DSLVGTYSKI306 MDHKNSLCFP316 EDAEISKHAK326 NLICAFLTDR336 EVRLGRNGVE 346 EIRQHPFFKN356 DQWHWDNIRE366 TAAPVVPELS376 SDIDSSNFDD386 IEDVETFPIP 400 KAFVGNQLPF410 IGFTYYR
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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 .VFA or .VFA2 or .VFA3 or :3VFA;style chemicals stick;color identity;select .A:98 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:105 or .A:106 or .A:119 or .A:121 or .A:122 or .A:123 or .A:136 or .A:140 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:221 or .A:231 or .A:232 or .A:384; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE98
3.516
ARG100
4.047
GLY101
3.603
ALA102
3.860
PHE103
3.264
GLY104
3.591
GLU105
3.724
VAL106
3.576
ALA119
3.517
LYS121
2.791
LEU122
3.905
LEU123
3.381
|
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| Ligand Name: N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-pyridin-4-ylpiperidine-1-carboxamide | Ligand Info | |||||
| Structure Description | ROCK2 IN COMPLEX WITH COMPOUND 12 | PDB:7P6N | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [5] |
| PDB Sequence |
ASRQRKLEAL
33 IRDPRSPINV43 ESLLDGLNSL53 VLDLDFPALR63 KNKNIDNFLN73 RYEKIVKKIR 83 GLQMKAEDYD93 VVKVIGRGAF103 GEVQLVRHKA113 SQKVYAMKLL123 SKFEMIKRSD 133 SAFFWEERDI143 MAFANSPWVV153 QLFYAFQDDR163 YLYMVMEYMP173 GGDLVNLMSN 183 YDVPEKWAKF193 YTAEVVLALD203 AIHSMGLIHR213 DVKPDNMLLD223 KHGHLKLADF 233 GTCMKMDETG243 MVHAVGTPDY256 ISPEVLKSQG266 FYGRECDWWS279 VGVFLYEMLV 289 GDTPFYADSL299 VGTYSKIMDH309 KNSLCFPEDA319 EISKHAKNLI329 CAFLTDREVR 339 LGRNGVEEIR349 QHPFFKNDQW359 HWDNIRETAA369 PVVPELSSDI379 DSSNFDDIED 389 VETFPIPKAF403 VGNQLPFIGF413 TYYR
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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 .5YS or .5YS2 or .5YS3 or :35YS;style chemicals stick;color identity;select .A:98 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:105 or .A:106 or .A:119 or .A:121 or .A:122 or .A:123 or .A:136 or .A:140 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:218 or .A:221 or .A:231 or .A:232 or .A:384; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE98
3.631
ARG100
3.956
GLY101
3.672
ALA102
3.396
PHE103
3.173
GLY104
3.755
GLU105
4.057
VAL106
3.737
ALA119
3.426
LYS121
2.597
LEU122
4.101
LEU123
3.531
|
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| Ligand Name: Methyl 3-[({2'-(Aminomethyl)-5'-[(3-Fluoropyridin-4-Yl)carbamoyl]biphenyl-3-Yl}carbonyl)amino]-4-Fluorobenzoate | Ligand Info | |||||
| Structure Description | ROCK2 IN COMPLEX WITH 1426382-07-1 | PDB:4WOT | ||||
| Method | X-ray diffraction | Resolution | 2.93 Å | Mutation | No | [6] |
| PDB Sequence |
AGASRQRKLE
31 ALIRDPRSPI41 NVESLLDGLN51 SLVLDLDFPA61 LRKNKNIDNF71 LNRYEKIVKK 81 IRGLQMKAED91 YDVVKVIGRG101 AFGEVQLVRH111 KASQKVYAMK121 LLSKFEMIKR 131 SDSAFFWEER141 DIMAFANSPW151 VVQLFYAFQD161 DRYLYMVMEY171 MPGGDLVNLM 181 SNYDVPEKWA191 KFYTAEVVLA201 LDAIHSMGLI211 HRDVKPDNML221 LDKHGHLKLA 231 DFGTCMKMDE241 TGMVHCVGTP254 DYISPEVLKS264 QGGDGFYGRE274 CDWWSVGVFL 284 YEMLVGDTPF294 YADSLVGTYS304 KIMDHKNSLC314 FPEDAEISKH324 AKNLICAFLT 334 DREVRLGRNG344 VEEIRQHPFF354 KNDQWHWDNI364 RETAAPVVPE374 LSSDIDSSNF 384 DDIEDVETFP398 IPKAFVGNQL408 PFIGFTYYR
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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 .3SG or .3SG2 or .3SG3 or :33SG;style chemicals stick;color identity;select .A:98 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:105 or .A:106 or .A:119 or .A:121 or .A:122 or .A:123 or .A:133 or .A:136 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:214 or .A:218 or .A:219 or .A:221 or .A:231 or .A:232 or .A:234 or .A:235 or .A:251 or .A:252 or .A:384; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE98
3.267
ARG100
4.576
GLY101
3.720
ALA102
3.656
PHE103
3.143
GLY104
3.847
GLU105
3.928
VAL106
3.540
ALA119
3.504
LYS121
3.862
LEU122
4.661
LEU123
3.730
ASP133
4.213
PHE136
3.197
VAL153
4.080
|
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| Ligand Name: N-[(1S)-2-hydroxy-1-phenylethyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A PHENYLPYRAZOLE AMIDE INHIBITOR | PDB:7JOV | ||||
| Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | No | [7] |
| PDB Sequence |
SRQRKLEALI
34 RDPRSPINVE44 SLLDGLNSLV54 LDLDFPALRK64 NKNIDNFLNR74 YEKIVKKIRG 84 LQMKAEDYDV94 VKVIGRGAFG104 EVQLVRHKAS114 QKVYAMKLLS124 KFEMIKRSDS 134 AFFWEERDIM144 AFANSPWVVQ154 LFYAFQDDRY164 LYMVMEYMPG174 GDLVNLMSNY 184 DVPEKWAKFY194 TAEVVLALDA204 IHSMGLIHRD214 VKPDNMLLDK224 HGHLKLADFG 234 TCMKMDETGM244 VHTPDYISPE260 VLKFYGRECD276 WWSVGVFLYE286 MLVGDTPFYA 296 DSLVGTYSKI306 MDHKNSLCFP316 EDAEISKHAK326 NLICAFLTDR336 EVRLGRNGVE 346 EIRQHPFFKN356 DQWHWDNIRE366 TAAPVVPELS376 SDIDSSNFDD386 IEDVETFPIP 400 KAFVGNQLPF410 IGFTYYR
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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 .VFS or .VFS2 or .VFS3 or :3VFS;style chemicals stick;color identity;select .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:105 or .A:106 or .A:119 or .A:121 or .A:122 or .A:123 or .A:140 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:218 or .A:221 or .A:231 or .A:232 or .A:384; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE98
3.687
GLY99
4.141
ARG100
3.254
GLY101
3.463
ALA102
4.526
PHE103
4.536
GLY104
3.566
GLU105
3.556
VAL106
3.397
ALA119
3.410
LYS121
2.773
LEU122
4.263
|
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| Ligand Name: (1s,4s)-4-(4-Fluorophenyl)-4-Hydroxy-6'-(5-Methyl-1h-Pyrazol-4-Yl)-1'h-Spiro[cyclohexane-1,2'-Thieno[3,2-D]pyrimidin]-4'(3'h)-One | Ligand Info | |||||
| Structure Description | Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative Pharmacophore Model: Synthesis and Biological Evaluation of 2,3-Dihydrothieno[3,2-d]pyrimidin-4(1H)-ones | PDB:5U7R | ||||
| Method | X-ray diffraction | Resolution | 3.33 Å | Mutation | No | [8] |
| PDB Sequence |
SRQRKLEALI
34 RDPRSPINVE44 SLLDGLNSLV54 LDLDFPALRK64 NKNIDNFLNR74 YEKIVKKIRG 84 LQMKAEDYDV94 VKVIGRGAFG104 EVQLVRHKAS114 QKVYAMKLLS124 KFEMIKRSDS 134 AFFWEERDIM144 AFANSPWVVQ154 LFYAFQDDRY164 LYMVMEYMPG174 GDLVNLMSNY 184 DVPEKWAKFY194 TAEVVLALDA204 IHSMGLIHRD214 VKPDNMLLDK224 HGHLKLADFG 234 TCMKMDETGM244 VHCDTAVGTP254 DYISPEVLKS264 QGGDGYYGRE274 CDWWSVGVFL 284 YEMLVGDTPF294 YADSLVGTYS304 KIMDHKNSLC314 FPEDAEISKH324 AKNLICAFLT 334 DREVRLGRNG344 VEEIRQHPFF354 KNDQWHWDNI364 RETAAPVVPE374 LSSDIDSSNF 384 DDIEETFPIP400 KAFVGNQLPF410 IGFTYYR
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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 .81G or .81G2 or .81G3 or :381G;style chemicals stick;color identity;select .A:98 or .A:99 or .A:100 or .A:101 or .A:106 or .A:119 or .A:121 or .A:140 or .A:153 or .A:169 or .A:170 or .A:171 or .A:172 or .A:176 or .A:178 or .A:216 or .A:218 or .A:219 or .A:221 or .A:231 or .A:232 or .A:384; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE98
3.666
GLY99
4.742
ARG100
3.811
GLY101
3.835
VAL106
3.857
ALA119
3.379
LYS121
2.932
GLU140
3.794
VAL153
3.894
MET169
3.721
GLU170
2.810
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 Inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Antitumor Agent. J Med Chem. 2020 Feb 13;63(3):1084-1104. | ||||
| REF 2 | Identification of Selective Dual ROCK1 and ROCK2 Inhibitors Using Structure-Based Drug Design. J Med Chem. 2018 Dec 27;61(24):11074-11100. | ||||
| REF 3 | Linking phenotype to kinase: identification of a novel benzoxaborole hinge-binding motif for kinase inhibition and development of high-potency rho kinase inhibitors. J Pharmacol Exp Ther. 2013 Dec;347(3):615-25. | ||||
| REF 4 | Identification of 5H-chromeno[3,4-c]pyridine and 6H-isochromeno[3,4-c]pyridine derivatives as potent and selective dual ROCK inhibitors. Bioorg Med Chem Lett. 2020 Nov 1;30(21):127474. | ||||
| REF 5 | Optimization of Rho kinase inhibitors towards potent, selective and CNS-penetrant molecules suitable for proof-of-concept studies in HD models | ||||
| REF 6 | Design, synthesis, and biological evaluation of novel, highly active soft ROCK inhibitors. J Med Chem. 2015 May 28;58(10):4309-24. | ||||
| REF 7 | Discovery of a phenylpyrazole amide ROCK inhibitor as a tool molecule for in vivo studies. Bioorg Med Chem Lett. 2020 Nov 1;30(21):127495. | ||||
| REF 8 | Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones. Bioorg Med Chem. 2017 Apr 1;25(7):2133-2147. | ||||
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