Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T88569 | Target Info | |||
| Target Name | Mutated oxalosuccinate decarboxylase (mIDH1) | ||||
| Synonyms | PICD (mutated); Oxalosuccinate decarboxylase (mutated); NADP(+)-specific ICDH (mutated); Isocitrate dehydrogenase [NADP] cytoplasmic (mutated); IDP (mutated); IDH (mutated); Cytosolic NADP-isocitrate dehydrogenase (mutated) | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | IDH1 | ||||
| Biochemical Class | Short-chain dehydrogenases reductase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: AG-881 | Ligand Info | |||||
| Structure Description | Crystal Structures of IDH1 R132H in complex with AG-881 | PDB:6ADG | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KL
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| Ligand Name: FT-2102 | Ligand Info | |||||
| Structure Description | Crystal structure of IDH1 R132H mutant in complex with FT-2102 | PDB:6U4J | ||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | Yes | [2] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLSLE
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ARG109
2.897
GLU110
3.994
ALA111
3.540
ILE113
3.639
ARG119
3.942
LEU120
3.050
VAL121
4.298
TRP124
3.684
LYS126
4.845
PRO127
3.440
ILE128
2.915
|
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| Ligand Name: IDH305 | Ligand Info | |||||
| Structure Description | IDH1 R132H mutant in complex with IDH305 | PDB:6B0Z | ||||
| Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | Yes | [3] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAATDFVVPG148 PGKVEITYTP158 SDGTQKVTYL 168 VHNFEEGGGV178 AMGMYNQDKS188 IEDFAHSSFQ198 MALSKGWPLY208 LSTKNTILKK 218 YDGRFKDIFQ228 EIYDKQYKSQ238 FEAQKIWYEH248 RLIDDMVAQA258 MKSEGGFIWA 268 CKNQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT313 RHYRMYQKGQ 323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS363 IETIEAGFMT 373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLAQA
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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 .C81 or .C812 or .C813 or :3C81;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:119 or .A:120 or .A:121 or .A:124 or .A:126 or .A:127 or .A:128 or .A:129 or .A:130 or .A:132 or .A:251 or .A:255 or .A:258 or .A:259 or .A:267 or .A:269 or .A:271 or .A:277 or .A:278 or .A:281 or .A:282 or .A:285 or .A:287 or .A:291; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG109
3.636
GLU110
4.117
ALA111
3.322
ILE113
3.912
ARG119
3.102
LEU120
3.070
VAL121
4.335
TRP124
3.162
LYS126
4.083
PRO127
3.878
ILE128
2.787
ILE129
4.965
ILE130
3.326
HIS132
3.005
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| Ligand Name: 3-Sulfinoalanine | Ligand Info | |||||
| Structure Description | Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor DS-1001B | PDB:7PJN | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | Yes | [4] |
| PDB Sequence |
SKKISGGSVV
11 EMQGDEMTRI21 IWELIKEKLI31 FPYVELDLHS41 YDLGIENRDA51 TNDQVTKDAA 61 EAIKKHNVGV71 KCATITPDEK81 RVEEFKLKQM91 WKSPNGTIRN101 ILGGTVFREA 111 IICKNIPRLV121 SGWVKPIIIG131 CHARATDFVV146 PGPGKVEITY156 TPSDGTQKVT 166 YLVHNFEEGG176 GVAMGMYNQD186 KSIEDFAHSS196 FQMALSKGWP206 LYLSTKNTIL 216 KKYDGRFKDI226 FQEIYDKQYK236 SQFEAQKIWY246 EHRLIDDMVA256 QAMKSEGGFI 266 WACKNYDGDV276 QSDFVAQGYG286 SLGMMTSVLV296 CPDGKTVEAE306 AAHGTVTRHY 316 RMYQKGQETS326 TNPIASIFAW336 TRGLAHRAKL346 DNNKELAFFA356 NALEEVSIET 366 IEAGFMTKDL376 AAIKGLPNVQ387 RSDYLNTFEF397 MDKLGENLKI407 KLAQ |
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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 .CSD or .CSD2 or .CSD3 or :3CSD;style chemicals stick;color identity;select .B:117 or .B:118 or .B:285 or .B:286 or .B:287 or .B:374 or .B:375 or .B:376 or .B:377 or .B:378 or .B:380 or .B:381 or .B:382; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Isocitric Acid | Ligand Info | |||||
| Structure Description | Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate | PDB:3MAP | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [5] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HARATDFVVP147 GPGKVEITYT157 PSDGTQKVTY 167 LVHNFEEGGG177 VAMGMYNQDK187 SIEDFAHSSF197 QMALSKGWPL207 YLSTKNTILK 217 KYDGRFKDIF227 QEIYDKQYKS237 QFEAQKIWYE247 HRLIDDMVAQ257 AMKSEGGFIW 267 ACKNVAQGYG286 SLGMMTSVLV296 CPDGKTVEAE306 AAHGTVTRHY316 RMYQKGQETS 326 TNPIASIFAW336 TRGLAHRAKL346 DNNKELAFFA356 NALEEVSIET366 IEAGFMTKDL 376 AACIKGLPNV386 QRSDYLNTFE396 FMDKLGENLK406 IKLAQAK
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .A:75 or .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109 or .A:308; 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: NADP+ | Ligand Info | |||||
| Structure Description | IDH1 R132H in complex with cpd 1 | PDB:4UMX | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | Yes | [6] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KL
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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 .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:277 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLU17
4.609
LYS72
3.421
CYS73
4.831
ALA74
3.502
THR75
2.904
ILE76
3.616
THR77
3.009
ARG82
3.005
ASN96
3.124
GLN277
3.397
SER287
4.642
LEU288
3.745
GLY289
3.668
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Alpha-ketoglutaric acid | Ligand Info | |||||
| Structure Description | Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase R132H mutant in complex with NADPH, ALPHA-KETOGLUTARATE and CALCIUM(2+) | PDB:3INM | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [7] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNIPRLVSG123 WVKPIIIGHH133 AYGDQYRATD143 FVVPGPGKVE153 ITYTPSDGTQ 163 KVTYLVHNFE173 EGGGVAMGMY183 NQDKSIEDFA193 HSSFQMALSK203 GWPLYLSTKN 213 TILKKYDGRF223 KDIFQEIYDK233 QYKSQFEAQK243 IWYEHRLIDD253 MVAQAMKSEG 263 GFIWACKNYD273 GDVQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT 313 RHYRMYQKGQ323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS 363 IETIEAGFMT373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLA |
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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 .AKG or .AKG2 or .AKG3 or :3AKG;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:100 or .A:109 or .A:139 or .A:275 or .A:278 or .A:308; 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: NADPH | Ligand Info | |||||
| Structure Description | Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase R132H mutant in complex with NADPH, ALPHA-KETOGLUTARATE and CALCIUM(2+) | PDB:3INM | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [7] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNIPRLVSG123 WVKPIIIGHH133 AYGDQYRATD143 FVVPGPGKVE153 ITYTPSDGTQ 163 KVTYLVHNFE173 EGGGVAMGMY183 NQDKSIEDFA193 HSSFQMALSK203 GWPLYLSTKN 213 TILKKYDGRF223 KDIFQEIYDK233 QYKSQFEAQK243 IWYEHRLIDD253 MVAQAMKSEG 263 GFIWACKNYD273 GDVQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT 313 RHYRMYQKGQ323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS 363 IETIEAGFMT373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLA |
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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 .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLU17
4.670
LYS72
3.699
CYS73
4.792
ALA74
3.546
THR75
2.840
ILE76
3.744
THR77
3.371
ARG82
3.026
ASN96
2.870
SER287
4.751
LEU288
3.515
GLY289
4.211
GLU306
4.684
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (2E)-3-{3-[3-(2,6-dichlorophenyl)-5-(propan-2-yl)-1,2-oxazole-4-carbonyl]-1-methyl-1H-indol-7-yl}prop-2-enoic acid | Ligand Info | |||||
| Structure Description | Human IDH1 R132C mutant complexed with compound A. | PDB:6IO0 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [8] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGC132 HRATDFVVPG148 PGKVEITYTP158 SDGTQKVTYL 168 VHNFEEGGGV178 AMGMYNQDKS188 IEDFAHSSFQ198 MALSKGWPLY208 LSTKNTILKK 218 YDGRFKDIFQ228 EIYDKQYKSQ238 FEAQKIWYEH248 RLIDDMVAQA258 MKSEGGFIWA 268 CKVQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT313 RHYRMYQKGQ 323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS363 IETIEAGFMT 373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLAQAK413 |
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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 .AOU or .AOU2 or .AOU3 or :3AOU;style chemicals stick;color identity;select .A:111 or .A:119 or .A:120 or .A:121 or .A:124 or .A:128 or .A:130 or .A:251 or .A:255 or .A:258 or .A:259 or .A:267 or .A:269 or .A:277 or .A:278 or .A:281 or .A:282 or .A:291; 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~{r},5~{s})-3-[6-(3-Methylbutoxy)-5-[[(1~{r},3~{s})-5-Oxidanyl-2-Adamantyl]carbamoyl]pyridin-2-Yl]-3-Azabicyclo[3.1.0]hexane-6-Carboxylic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of Iso-citrate Dehydrogenase R132H in complex with a novel inhibitor (compound 13a) | PDB:5L57 | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | Yes | [9] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDAAR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 TYLVHNFEEG175 GGVAMGMYNQ185 DKSIEDFAHS195 SFQMALSKGW205 PLYLSTKNTI 215 LKKYDGRFKD225 IFQEIYDKQY235 KSQFAAAAIW245 YEHRLIDDMV255 AQAMKSEGGF 265 IWACKNYDGD275 VQSDSVAQGY285 GSLGMMTSVL295 VCPDGKTVEA305 EAAHGTVTRH 315 YRMYQKGQET325 STNPIASIFA335 WTRGLAHRAK345 LDNNKELAFF355 ANALEEVSIE 365 TIEAGFMTKD375 LAACIKGLPN385 VQRSDYLNTF395 EFMDKLGENL405 KIKLAQAKL |
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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 .6N3 or .6N32 or .6N33 or :36N3;style chemicals stick;color identity;select .A:111 or .A:113 or .A:119 or .A:120 or .A:124 or .A:128 or .A:130 or .A:132 or .A:251 or .A:255 or .A:258 or .A:259 or .A:267 or .A:269 or .A:271 or .A:281 or .A:285 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-[(3~{r})-1-[6-Cyclohexylsulfanyl-5-[[(1~{r},3~{s})-5-Oxidanyl-2-Adamantyl]carbamoyl]pyridin-2-Yl]pyrrolidin-3-Yl]ethanoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of Iso-citrate Dehydrogenase 1 [IDH1 (R132H)] in complex with a novel inhibitor (Compound 2) | PDB:5L58 | ||||
| Method | X-ray diffraction | Resolution | 3.04 Å | Mutation | Yes | [9] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDAAR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGATDFVV146 PGPEITTYLV169 GGVAMGMYNQ 185 DKSIEDFAHS195 SFQMALSKGW205 PLYLSTKKYD220 GRFKDIFQEI230 YDKQYKSQFA 240 AAAIWYEHRL250 IDDMVAQAMK260 SEGGFIWACK270 NYVAQGYGSL288 GMMTSVLVCP 298 DGKTVEAEAA308 HGTVTRHYRM318 YQKGQETSTN328 PIASIFAWTR338 GLAHRAKLDN 348 NKELAFFANA358 LEEVSIETIE368 AGFMTKDLAA378 CIKGLPNVQR388 SDYLNTFEFM 398 DKLGENLKIK408 LAQAKL
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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 .6MX or .6MX2 or .6MX3 or :36MX;style chemicals stick;color identity;select .A:111 or .A:119 or .A:120 or .A:124 or .A:128 or .A:130 or .A:132 or .A:251 or .A:255 or .A:258 or .A:259 or .A:267 or .A:269 or .A:271 or .A:285 or .A:291; 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-[(E)-(1-Methyl-5-Oxo-2-Thioxoimidazolidin-4-Ylidene)methyl]pyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of a metabolic reductase with (E)-5-((1-methyl-5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)pyridin-2(1H)-one | PDB:4XRX | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | Yes | [10] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HYRATDFVVP147 GPGKVEITYT157 PSDGTQKVTY 167 LVHNFEEGGG177 VAMGMYNQDK187 SIEDFAHSSF197 QMALSKGWPL207 YLSTKNTILK 217 KYDGRFKDIF227 QEIYDKQYKS237 QFEAQKIWYE247 HRLIDDMVAQ257 AMKSEGGFIW 267 ACKSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT313 RHYRMYQKGQ323 ETSTNPIASI 333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS363 IETIEAGFMT373 KDLAACIKGL 383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLAQAK413
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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 .42V or .42V2 or .42V3 or :342V;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:101 or .A:140; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: (E)-1-Benzyl-5-((1-Methyl-5-Oxo-2-Thioxoimidazolidin-4-Ylidene)methyl)pyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of a metabolic reductase with (E)-1-benzyl-5-((1-methyl-5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)pyridin-2(1H)-one | PDB:4XS3 | ||||
| Method | X-ray diffraction | Resolution | 3.29 Å | Mutation | Yes | [10] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRKPI128 IIGHHYRATD143 FVVPGPGKVE153 ITYTPSDGTQ163 KVTYLVHNFE 173 EGGGVAMGMY183 NQDKSIEDFA193 HSSFQMALSK203 GWPLYLSTKN213 TILKKYDGRF 223 KDIFQEIYDK233 QYKSQFEAQK243 IWYEHRLIDD253 MVAQAMKSEG263 GFIWACKSLG 289 MMTSVLVCPD299 GKTVEAEAAH309 GTVTRHYRMY319 QKGQETSTNP329 IASIFAWTRG 339 LAHRAKLDNN349 KELAFFANAL359 EEVSIETIEA369 GFMTKDLAAC379 IKGLPNVQRS 389 DYLNTFEFMD399 KLGENLKIKL409 AQA
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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 .42W or .42W2 or .42W3 or :342W;style chemicals stick;color identity;select .A:77 or .A:93 or .A:94 or .A:96 or .A:97 or .A:100 or .A:101 or .A:109; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-Benzyl-1-Hydroxy-4-Methylpyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of a metabolic reductase with 6-benzyl-1-hydroxy-4-methylpyridin-2(1H)-one | PDB:4I3L | ||||
| Method | X-ray diffraction | Resolution | 3.29 Å | Mutation | Yes | [11] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNPIIIGHH133 ATDFVVPGPG150 KVEITYTPSD160 GTQKVTYLVH170 NFEEGGGVAM 180 GMYNQDKSIE190 DFAHSSFQMA200 LSKGWPLYLS210 TKNTILKKYD220 GRFKDIFQEI 230 YDKQYKSQFE240 AQKIWYEHRL250 IDDMVGFIWA268 CKNLGMMTSV294 LVCPDGKTVE 304 AEAAHGTVTR314 HYRMYQKGQE324 TSTNPIASIF334 AWTRGLAHRA344 KLDNNKELAF 354 FANALEEVSI364 ETIEAGFMTK374 DLAACIKGLP384 NVQRSDYLNT394 FEFMDKLGEN 404 LKIKLAQ
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .1BZ or .1BZ2 or .1BZ3 or :31BZ;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (2~{R})-2-[2-[(3~{R})-3-(4-fluorophenyl)pyrrolidin-1-yl]ethyl]-1,4-dimethyl-piperazine | Ligand Info | |||||
| Structure Description | Crystal structure of IDH1 R132H in complex with HMS101 | PDB:6Q6F | ||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | Yes | [12] |
| PDB Sequence |
MSKKISGGSV
10 VEMQGDEMTR20 IIWELIKEKL30 IFPYVELDLH40 SYDLGIENRD50 ATNDQVTKDA 60 AEAIKKHNVG70 VKCATITPDE80 KRVEEFKLKQ90 MWKSPNGTIR100 NILGGTVFRE 110 AIICKNIPRL120 VSGWVKPIII130 GHHAYGDQYR140 ATDFVVPGPG150 KVEITYTPSD 160 GTQKVTYLVH170 NFEEGGGVAM180 GMYNQDKSIE190 DFAHSSFQMA200 LSKGWPLYLS 210 TKNTILKKYD220 GRFKDIFQEI230 YDKQYKSQFE240 AQKIWYEHRL250 IDDMVAQAMK 260 SEGGFIWACK270 NGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV312 TRHYRMYQKG 322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV362 SIETIEAGFM 372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA412 KL |
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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 .HJQ or .HJQ2 or .HJQ3 or :3HJQ;style chemicals stick;color identity;select .A:287 or .A:288 or .A:289 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:327 or .A:328 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-Hydroxy-6-(4-Hydroxybenzyl)-4-Methylpyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-one | PDB:4I3K | ||||
| Method | X-ray diffraction | Resolution | 3.31 Å | Mutation | Yes | [11] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNPIIIGHH133 ATDFVVPGPG150 KVEITYTPSD160 GTQKVTYLVH170 NFEEGGGVAM 180 GMYNQDKSIE190 DFAHSSFQMA200 LSKGWPLYLS210 TKNTILKKYD220 GRFKDIFQEI 230 YDKQYKSQFE240 AQKIWYEHRL250 IDDMVGFIWA268 CKNLGMMTSV294 LVCPDGKTVE 304 AEAAHGTVTR314 HYRMYQKGQE324 TSTNPIASIF334 AWTRGLAHRA344 KLDNNKELAF 354 FANALEEVSI364 ETIEAGFMTK374 DLAACIKGLP384 NVQRSDYLNT394 FEFMDKLGEN 404 LKIKLAQ
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .1BX or .1BX2 or .1BX3 or :31BX;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109 or .A:308; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (R)-1-(4-fluorobenzyl)-N-(3-((S)-1-hydroxyethyl)phenyl)-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of human IDH1 in complex with GSK321A | PDB:5DE1 | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [13] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HRATDFVVPG148 PGKVEITYTP158 SDGTQKVTYL 168 VHNFEEGGGV178 AMGMYNQDKS188 IEDFAHSSFQ198 MALSKGWPLY208 LSTKNTILKK 218 YDGRFKDIFQ228 EIYDKQYKSQ238 FEAQKIWYEH248 RLIDDMVAQA258 MKSEGGFIWA 268 CKNDSVAQGY285 GSLGMMTSVL295 VCPDGKTVEA305 EAAHGTVTRH315 YRMYQKGQET 325 STNPIASIFA335 WTRGLAHRAK345 LDNNKELAFF355 ANALEEVSIE365 TIEAGFMTKD 375 LAACIKGLPN385 VQRSDYLNTF395 EFMDKLGENL405 KIKLAQAKL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .59D or .59D2 or .59D3 or :359D;style chemicals stick;color identity;select .A:111 or .A:113 or .A:118 or .A:119 or .A:120 or .A:124 or .A:125 or .A:126 or .A:127 or .A:128 or .A:130 or .A:255 or .A:259 or .A:267 or .A:281 or .A:282 or .A:284 or .A:285 or .A:291 or .A:379; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ALA111
3.838
ILE113
3.441
PRO118
3.841
ARG119
3.248
LEU120
2.845
TRP124
3.612
VAL125
4.867
LYS126
3.629
PRO127
3.773
ILE128
2.839
|
|||||
| Ligand Name: (S)-3-(2-(((S)-1-(5-(4-Fluoro-3-methylphenyl)pyrimidin-2-YL)ethyl)amino)pyrimidin-4-YL)-4-isopropyloxazolidin-2-one | Ligand Info | |||||
| Structure Description | IDH1 R132H mutant in complex with IDH889 | PDB:5TQH | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [14] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAQYRATDFV145 VPGPGKVEIT155 YTPSDGTQKV 165 TYLVHNFEEG175 GGVAMGMYNQ185 DKSIEDFAHS195 SFQMALSKGW205 PLYLSTKNTI 215 LKKYDGRFKD225 IFQEIYDKQY235 KSQFEAQKIW245 YEHRLIDDMV255 AQAMKSEGGF 265 IWACKNSDSV281 AQGYGSLGMM291 TSVLVCPDGK301 TVEAEAAHGT311 VTRHYRMYQK 321 GQETSTNPIA331 SIFAWTRGLA341 HRAKLDNNKE351 LAFFANALEE361 VSIETIEAGF 371 MTKDLAACIK381 GLPNVQRSDY391 LNTFEFMDKL401 GENLKIKLAQ411 A |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7J2 or .7J22 or .7J23 or :37J2;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:119 or .A:120 or .A:121 or .A:124 or .A:126 or .A:127 or .A:128 or .A:130 or .A:255 or .A:258 or .A:259 or .A:267 or .A:278 or .A:281 or .A:282 or .A:285 or .A:287 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG109
3.454
GLU110
4.135
ALA111
3.281
ILE113
3.889
ARG119
3.101
LEU120
2.837
VAL121
4.116
TRP124
3.494
LYS126
4.032
PRO127
3.671
ILE128
2.817
|
|||||
| Ligand Name: (4s)-3-(2-{[(1s)-1-Phenylethyl]amino}pyrimidin-4-Yl)-4-(Propan-2-Yl)-1,3-Oxazolidin-2-One | Ligand Info | |||||
| Structure Description | IDH1 R132H in complex with IDH125 | PDB:5SVF | ||||
| Method | X-ray diffraction | Resolution | 2.34 Å | Mutation | Yes | [15] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNIPRLVSG123 WVKPIIIGHH133 AATDFVVPGP149 GKVEITYTPS159 DGTQKVTYLV 169 HNFEEGGGVA179 MGMYNQDKSI189 EDFAHSSFQM199 ALSKGWPLYL209 STKNTILKKY 219 DGRFKDIFQE229 IYDKQYKSQF239 EAQKIWYEHR249 LIDDMVAQAM259 KSEGGFIWAC 269 KNQSDSVAQG284 YGSLGMMTSV294 LVCPDGKTVE304 AEAAHGTVTR314 HYRMYQKGQE 324 TSTNPIASIF334 AWTRGLAHRA344 KLDNNKELAF354 FANALEEVSI364 ETIEAGFMTK 374 DLAACIKGLP384 NVQRSDYLNT394 FEFMDKLGEN404 LKIKLAQA
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .70P or .70P2 or .70P3 or :370P;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:118 or .A:119 or .A:120 or .A:121 or .A:124 or .A:126 or .A:127 or .A:128 or .A:129 or .A:130 or .A:278 or .A:281 or .A:282 or .A:285 or .A:287 or .A:291; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG109
3.317
GLU110
3.884
ALA111
3.233
ILE113
3.720
PRO118
4.938
ARG119
3.080
LEU120
3.046
VAL121
3.746
TRP124
3.645
LYS126
3.895
|
|||||
| Ligand Name: 3-Benzyl-N-[3-(Dimethylsulfamoyl)phenyl]-4-Oxo-3,4-Dihydrophthalazine-1-Carboxamide | Ligand Info | |||||
| Structure Description | IDH1 R132H in complex with IDH146 | PDB:5SUN | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | Yes | [15] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 ATDFVVPGPG150 KVEITYTPSD160 GTQKVTYLVH 170 NFEEGGGVAM180 GMYNQDKSIE190 DFAHSSFQMA200 LSKGWPLYLS210 TKNTILKKYD 220 GRFKDIFQEI230 YDKQYKSQFE240 AQKIWYEHRL250 IDDMVAQAMK260 SEGGFIWACK 270 NSLGMMTSVL295 VCPDGKTVEA305 EAAHGTVTRH315 YRMYQKGQET325 STNPIASIFA 335 WTRGLAHRAK345 LDNNKELAFF355 ANALEEVSIE365 TIEAGFMTKD375 LAACIKGLPN 385 VQRSDYLNTF395 EFMDKLGENL405 KIKLAQAK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .70Q or .70Q2 or .70Q3 or :370Q;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:120 or .A:124 or .A:126 or .A:127 or .A:128 or .A:129 or .A:130 or .A:255 or .A:258 or .A:259 or .A:261 or .A:262 or .A:263 or .A:264 or .A:265 or .A:267 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG109
3.140
GLU110
3.761
ALA111
3.591
ILE113
3.851
LEU120
4.876
TRP124
3.062
LYS126
3.034
PRO127
3.939
ILE128
3.250
ILE129
4.772
ILE130
3.567
|
|||||
| Ligand Name: (R)-3-butyl-2-oxopentanedioic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of IDH1 variant R132C S280F in complex with NADPH, Ca2+ and 3-butyl-2-oxoglutarate | PDB:8BAY | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | Yes | [16] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGC132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDFVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLLE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .QDC or .QDC2 or .QDC3 or :3QDC;style chemicals stick;color identity;select .A:77 or .A:94 or .A:95 or .A:96 or .A:97 or .A:100 or .A:109 or .A:139 or .A:275 or .A:306 or .A:308; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (S)-3-butyl-2-oxopentanedioic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of IDH1 variant R132C S280F in complex with NADPH, Ca2+ and 3-butyl-2-oxoglutarate | PDB:8BAY | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | Yes | [16] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGC132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDFVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLLE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .QD8 or .QD82 or .QD83 or :3QD8;style chemicals stick;color identity;select .A:77 or .A:94 or .A:95 or .A:96 or .A:97 or .A:100 or .A:109 or .A:139 or .A:275 or .A:306 or .A:308; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Safusidenib | Ligand Info | |||||
| Structure Description | Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor DS-1001B | PDB:7PJN | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | Yes | [4] |
| PDB Sequence |
> Chain A
KKISGGSVVE 12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGC132 HAYRATDFVV146 PGPGKVEITY156 TPSDGTQKVT 166 YLVHNFEEGG176 GVAMGMYNQD186 KSIEDFAHSS196 FQMALSKGWP206 LYLSTKNTIL 216 KKYDGRFKDI226 FQEIYDKQYK236 SQFEAQKIWY246 EHRLIDDMVA256 QAMKSEGGFI 266 WACKNYDGDV276 QSDFVAQGYG286 SLGMMTSVLV296 CPDGKTVEAE306 AAHGTVTRHY 316 RMYQKGQETS326 TNPIASIFAW336 TRGLAHRAKL346 DNNKELAFFA356 NALEEVSIET 366 IEAGFMTKDL376 AACIKGLPNV386 QRSDYLNTFE396 FMDKLGENLK406 IKLAQA > Chain B SKKISGGSVV 11 EMQGDEMTRI21 IWELIKEKLI31 FPYVELDLHS41 YDLGIENRDA51 TNDQVTKDAA 61 EAIKKHNVGV71 KCATITPDEK81 RVEEFKLKQM91 WKSPNGTIRN101 ILGGTVFREA 111 IICKNIPRLV121 SGWVKPIIIG131 CHARATDFVV146 PGPGKVEITY156 TPSDGTQKVT 166 YLVHNFEEGG176 GVAMGMYNQD186 KSIEDFAHSS196 FQMALSKGWP206 LYLSTKNTIL 216 KKYDGRFKDI226 FQEIYDKQYK236 SQFEAQKIWY246 EHRLIDDMVA256 QAMKSEGGFI 266 WACKNYDGDV276 QSDFVAQGYG286 SLGMMTSVLV296 CPDGKTVEAE306 AAHGTVTRHY 316 RMYQKGQETS326 TNPIASIFAW336 TRGLAHRAKL346 DNNKELAFFA356 NALEEVSIET 366 IEAGFMTKDL376 AAIKGLPNVQ387 RSDYLNTFEF397 MDKLGENLKI407 KLAQ |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7SU or .7SU2 or .7SU3 or :37SU;style chemicals stick;color identity;select .A:111 or .A:113 or .A:119 or .A:120 or .A:121 or .A:124 or .A:127 or .A:128 or .A:130 or .A:132 or .A:251 or .A:255 or .A:258 or .A:259 or .A:265 or .A:267 or .A:269 or .A:271 or .A:275 or .A:276 or .A:277 or .A:278 or .A:279 or .A:281 or .A:282 or .A:283 or .A:287 or .A:291 or .B:111 or .B:113 or .B:119 or .B:120 or .B:121 or .B:124 or .B:127 or .B:128 or .B:130 or .B:132 or .B:210 or .B:251 or .B:255 or .B:258 or .B:259 or .B:265 or .B:267 or .B:269 or .B:271 or .B:276 or .B:277 or .B:278 or .B:279 or .B:281 or .B:282 or .B:287 or .B:291; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ALA111[A]
2.961
ILE113[A]
4.475
ARG119[A]
1.735
LEU120[A]
2.748
VAL121[A]
2.705
TRP124[A]
2.439
PRO127[A]
4.344
ILE128[A]
2.743
ILE130[A]
2.251
CYS132[A]
3.612
ILE251[A]
3.990
VAL255[A]
2.691
ALA258[A]
3.174
MET259[A]
2.388
PHE265[A]
4.371
TRP267[A]
2.524
CYS269[A]
3.868
ASN271[A]
2.982
ASP275[A]
4.957
VAL276[A]
2.970
GLN277[A]
3.794
SER278[A]
2.244
ASP279[A]
4.842
VAL281[A]
2.042
ALA282[A]
2.030
GLN283[A]
4.871
SER287[A]
3.422
MET291[A]
3.485
ALA111[B]
2.754
ILE113[B]
3.216
ARG119[B]
1.515
LEU120[B]
2.893
VAL121[B]
2.684
TRP124[B]
2.589
PRO127[B]
4.939
ILE128[B]
2.306
ILE130[B]
2.210
CYS132[B]
3.646
SER210[B]
4.732
ILE251[B]
3.311
VAL255[B]
2.728
ALA258[B]
3.335
MET259[B]
2.497
PHE265[B]
4.305
TRP267[B]
2.437
CYS269[B]
2.652
ASN271[B]
3.874
VAL276[B]
3.723
GLN277[B]
3.955
SER278[B]
2.216
ASP279[B]
4.636
VAL281[B]
2.118
ALA282[B]
2.512
SER287[B]
3.832
MET291[B]
2.980
|
|||||
| Ligand Name: 2,6-Bis(1h-Imidazol-1-Ylmethyl)-4-(2,4,4-Trimethylpentan-2-Yl)phenol | Ligand Info | |||||
| Structure Description | IDH1 R132H in complex with cpd 1 | PDB:4UMX | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | Yes | [6] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KL
|
|||||
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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 .VVS or .VVS2 or .VVS3 or :3VVS;style chemicals stick;color identity;select .A:111 or .A:120 or .A:124 or .A:128 or .A:130 or .A:254 or .A:255 or .A:258 or .A:259 or .A:265 or .A:267 or .A:279 or .A:280 or .A:281 or .A:282 or .A:285 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3,6,9,12,15,18,21,24,27,30,33,36-Dodecaoxaoctatriacontane-1,38-diol | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Cytosolic Isocitrate Dehydrogenase (IDH1) R132H Mutant in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor | PDB:6VEI | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [17] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLS
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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 .33O or .33O2 or .33O3 or :333O;style chemicals stick;color identity;select .A:14 or .A:20 or .A:21 or .A:24 or .A:25 or .A:28 or .A:43 or .A:47 or .A:85 or .A:86 or .A:316 or .A:320 or .A:321; 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-{[(6-Chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-methylpyridine-3-carbonitrile | Ligand Info | |||||
| Structure Description | Crystal structure of IDH1 R132H mutant in complex with compound 32 | PDB:6O2Z | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [18] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HADQYRATDF144 VVPGPGKVEI154 TYTPSDGTQK 164 VTYLVHNFEE174 GGGVAMGMYN184 QDKSIEDFAH194 SSFQMALSKG204 WPLYLSTKNT 214 ILKKYDGRFK224 DIFQEIYDKQ234 YKSQFEAQKI244 WYEHRLIDDM254 VAQAMKSEGG 264 FIWACKNYDG274 DVQSDSVAQG284 YGSLGMMTSV294 LVCPDGKTVE304 AEAAHGTVTR 314 HYRMYQKGQE324 TSTNPIASIF334 AWTRGLAHRA344 KLDNNKELAF354 FANALEEVSI 364 ETIEAGFMTK374 DLAACIKGLP384 NVQRSDYLNT394 FEFMDKLGEN404 LKIKLAQAKL 414 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 .LJV or .LJV2 or .LJV3 or :3LJV;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:119 or .A:120 or .A:124 or .A:126 or .A:128 or .A:130 or .A:258 or .A:259 or .A:267 or .A:279 or .A:281 or .A:282 or .A:284 or .A:285 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-{[(6-Chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-methoxybenzonitrile | Ligand Info | |||||
| Structure Description | Crystal structure of IDH1 R132H mutant in complex with compound 24 | PDB:6O2Y | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [18] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLE
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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 .LJY or .LJY2 or .LJY3 or :3LJY;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:113 or .A:119 or .A:120 or .A:121 or .A:124 or .A:126 or .A:128 or .A:130 or .A:255 or .A:258 or .A:259 or .A:267 or .A:279 or .A:281 or .A:282 or .A:285 or .A:291; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG109
2.814
GLU110
4.346
ALA111
3.708
ILE113
3.583
ARG119
3.289
LEU120
3.280
VAL121
4.872
TRP124
3.598
LYS126
4.497
ILE128
3.297
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2. Biochem Biophys Res Commun. 2018 Sep 18;503(4):2912-2917. | ||||
| REF 2 | Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor. J Med Chem. 2020 Feb 27;63(4):1612-1623. | ||||
| REF 3 | Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. ACS Med Chem Lett. 2017 Sep 18;8(10):1116-1121. | ||||
| REF 4 | Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors. Nat Commun. 2022 Aug 15;13(1):4785. | ||||
| REF 5 | Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H. Cell Res. 2010 Nov;20(11):1188-200. | ||||
| REF 6 | Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption of a metal binding network by an allosteric small molecule. J Biol Chem. 2015 Jan 9;290(2):762-74. | ||||
| REF 7 | Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009 Dec 10;462(7274):739-44. | ||||
| REF 8 | A Potent Blood-Brain Barrier-Permeable Mutant IDH1 Inhibitor Suppresses the Growth of Glioblastoma with IDH1 Mutation in a Patient-Derived Orthotopic Xenograft Model. Mol Cancer Ther. 2020 Feb;19(2):375-383. | ||||
| REF 9 | Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells. J Med Chem. 2016 Dec 22;59(24):11120-11137. | ||||
| REF 10 | Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds. J Med Chem. 2015 Sep 10;58(17):6899-6908. | ||||
| REF 11 | Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase. ACS Med Chem Lett. 2013 Jun 13;4(6):542-546. | ||||
| REF 12 | In vivo efficacy of mutant IDH1 inhibitor HMS-101 and structural resolution of distinct binding site. Leukemia. 2020 Feb;34(2):416-426. | ||||
| REF 13 | New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86. | ||||
| REF 14 | Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1. ACS Med Chem Lett. 2016 Dec 16;8(2):151-156. | ||||
| REF 15 | Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity. Structure. 2017 Mar 7;25(3):506-513. | ||||
| REF 16 | Natural and synthetic 2-oxoglutarate derivatives are substrates for oncogenic variants of human isocitrate dehydrogenase 1 and 2. J Biol Chem. 2023 Feb;299(2):102873. | ||||
| REF 17 | Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma. ACS Med Chem Lett. 2020 Jan 22;11(2):101-107. | ||||
| REF 18 | Discovery and Optimization of Quinolinone Derivatives as Potent, Selective, and Orally Bioavailable Mutant Isocitrate Dehydrogenase 1 (mIDH1) Inhibitors. J Med Chem. 2019 Jul 25;62(14):6575-6596. | ||||
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