Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T27861 | Target Info | |||
| Target Name | Protein cereblon (CRBN) | ||||
| Synonyms | Protein cereblon | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CRBN | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: CC-220 | Ligand Info | |||||
| Structure Description | Cereblon in complex with DDB1 and CC-220 | PDB:5V3O | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [1] |
| PDB Sequence |
INFDTSLPTS
56 HTYLGADMEE66 FHGRTLHDDD76 SCQVIPVLPQ86 VMMILIPGQT96 LPLQLFHPQE 106 VSMVRNLIQK116 DRTFAVLAYS126 AQFGTTAEIY142 AYREEQDFGI152 EIVKVKAIGR 162 QRFKVLELRT172 QSDGIQQAKV182 QILPECVLPS192 TMSAVQLESL202 NKCQIFPSSY 221 KWWQKYQKRK231 FHCANLTSWP241 RWLYSLYDAE251 TLMDRIKKQL261 REWDDDSLPS 275 NPIDFSYRVA285 ACLPIDDVLR295 IQLLKIGSAI305 QRLRCELDIM315 NKCTSLCCKQ 325 CQETEITTKN335 EIFSLSLCGP345 MAAYVNPHGY355 VHETLTVYKA365 CNLNLIGRPS 375 TEHSWFPGYA385 WTVAQCKICA395 SHIGWKFTAT405 KKDMSPQKFW415 GLTRSALLPT 425 IPD
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Mezigdomide | Ligand Info | |||||
| Structure Description | Cereblon~DDB1 bound to CC-92480 with DDB1 in the linear conformation | PDB:8D7U | ||||
| Method | Electron microscopy | Resolution | 3.10 Å | Mutation | No | [2] |
| PDB Sequence |
KKPNIINFDT
51 SLPTSHTYLG61 ADMEEFHGRT71 LHDDDSCQVI81 PVLPQVMMIL91 IPGQTLPLQL 101 FHPQEVSMVR111 NLIQKDRTFA121 VLAYSNVQER131 EAQFGTTAEI141 YAYREEQDFG 151 IEIVKVKAIG161 RQRFKVLELR171 TQSDGIQQAK181 VQILPECVLP191 STMSAVQLES 201 LNKCQIFPSK211 PVSREDQCSY221 KWWQKYQKRK231 FHCANLTSWP241 RWLYSLYDAE 251 TLMDRIKKQL261 REWDENLKDD271 SLPSNPIDFS281 YRVAACLPID291 DVLRIQLLKI 301 GSAIQRLRCE311 LDIMNKCTSL321 CCKQCQETEI331 TTKNEIFSLS341 LCGPMAAYVN 351 PHGYVHETLT361 VYKACNLNLI371 GRPSTEHSWF381 PGYAWTVAQC391 KICASHIGWK 401 FTATKKDMSP411 QKFWGLTRSA421 LLPT
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: S-Lenalidomide | Ligand Info | |||||
| Structure Description | Structural basis of Lenalidomide induced CK1a degradation by the crl4crbn ubiquitin ligase | PDB:5FQD | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | No | [3] |
| PDB Sequence |
INFDTSLPTS
56 HTYLGADMEE66 FHGRTLHDDD76 SCQVIPVLPQ86 VMMILIPGQT96 LPLQLFHPQE 106 VSMVRNLIQK116 DRTFAVLAYS126 NVQEREAQFG136 TTAEIYAYRE146 EQDFGIEIVK 156 VKAIGRQRFK166 VLELRTQSDG176 IQQAKVQILP186 ECVLPSTMSA196 VQLESLNKCQ 206 IFPCSYKWWQ225 KYQKRKFHCA235 NLTSWPRWLY245 SLYDAETLMD255 RIKKQLREWD 265 ENLKDDSLPS275 NPIDFSYRVA285 ACLPIDDVLR295 IQLLKIGSAI305 QRLRCELDIM 315 NKCTSLCCKQ325 CQETEITTKN335 EIFSLSLCGP345 MAAYVNPHGY355 VHETLTVYKA 365 CNLNLIGRPS375 TEHSWFPGYA385 WTVAQCKICA395 SHIGWKFTAT405 KKDMSPQKFW 415 GLTRSALLPT425 IPDTEDEISP435 D
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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 .LVY or .LVY2 or .LVY3 or :3LVY;style chemicals stick;color identity;select .B:350 or .B:351 or .B:352 or .B:353 or .B:357 or .B:377 or .B:378 or .B:379 or .B:380 or .B:381 or .B:386 or .B:400 or .B:402; 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: Pomalidomide, (S)- | Ligand Info | |||||
| Structure Description | Structure of DDB1-CRBN-pomalidomide complex bound to IKZF1(ZF2) | PDB:6H0F | ||||
| Method | X-ray diffraction | Resolution | 3.25 Å | Mutation | No | [4] |
| PDB Sequence |
GRTLHDDDSC
78 QVIPVLPQVM88 MILIPGQTLP98 LQLFHPQEVS108 MVRNLIQKDR118 TFAVLAYSNV 128 QEREAQFGTT138 AEIYAYREEQ148 DFGIEIVKVK158 AIGRQRFKVL168 ELRTQSDGIQ 178 QAKVQILPEC188 VLPSTMSAVQ198 LESLNKCQIF208 PSKPVSREDQ218 CSYKWWQKYQ 228 KRKFHCANLT238 SWPRWLYSLY248 DAETLMDRIK258 KQLREWDENL268 KDDSLPSNPI 278 DFSYRVAACL288 PIDDVLRIQL298 LKIGSAIQRL308 RCELDIMNKC318 TSLCCKQCQE 328 TEITTKNEIF338 SLSLCGPMAA348 YVNPHGYVHE358 TLTVYKACNL368 NLIGRPSTEH 378 SWFPGYAWTV388 AQCKICASHI398 GWKFTATKKD408 MSPQKFWGLT418 RSALLPTIPD 428 TEDEISPDKV438 ILCL
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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 .Y70 or .Y702 or .Y703 or :3Y70;style chemicals stick;color identity;select .B:350 or .B:351 or .B:352 or .B:353 or .B:357 or .B:375 or .B:377 or .B:378 or .B:379 or .B:380 or .B:381 or .B:386 or .B:388 or .B:400 or .B:402; color #f3c393; 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: 2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(8-{[({2-[(3S)-2,6-dioxopiperidin-3-yl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}oxy)acetyl]amino}octyl)acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of DDB1-CRBN-BRD4(BD1) complex bound to dBET6 PROTAC. | PDB:6BOY | ||||
| Method | X-ray diffraction | Resolution | 3.33 Å | Mutation | Yes | [5] |
| PDB Sequence |
PNIINFDTSL
53 PTSHTYLGAD63 MEEFHGRTLH73 DDDSCQVIPV83 LPQVMMILIP93 GQTLPLQLFH 103 PQEVSMVRNL113 IQKDRTFAVL123 AYSNVQEREA133 QFGTTAEIYA143 YREEQDFGIE 153 IVKVKAIGRQ163 RFKVLELRTQ173 SDGIQQAKVQ183 ILPECVLPST193 MSAVQLESLN 203 KCQIFPCSYK222 WWQKYQKRKF232 HCANLTSWPR242 WLYSLYDAET252 LMDRIKKQLR 262 EWDENLKDDS272 LPSNPIDFSY282 RVAACLPIDD292 VLRIQLLKIG302 SAIQRLRCEL 312 DIMNKCTSLC322 CKQCQETEIT332 TKNEIFSLSL342 CGPMAAYVNP352 HGYVHETLTV 362 YKACNLNLIG372 RPSTEHSWFP382 GYAWTVAQCK392 ICASHIGWKF402 TATKKDMSPQ 412 KFWGLTRSAL422 LPTIP
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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 .RN6 or .RN62 or .RN63 or :3RN6;style chemicals stick;color identity;select .B:350 or .B:351 or .B:352 or .B:353 or .B:355 or .B:357 or .B:377 or .B:378 or .B:379 or .B:380 or .B:381 or .B:386 or .B:400 or .B:402; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: methyl {(6S)-4-(4-chlorophenyl)-2-[(8-{[({2-[(3S)-2,6-dioxopiperidin-3-yl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}oxy)acetyl]amino}octyl)carbamoyl]-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate | Ligand Info | |||||
| Structure Description | Crystal structure of DDB1-CRBN-BRD4(BD1) complex bound to dBET23 PROTAC. | PDB:6BN7 | ||||
| Method | X-ray diffraction | Resolution | 3.50 Å | Mutation | Yes | [5] |
| PDB Sequence |
PNIINFDTSL
53 PTSHTYLGAD63 MEEFHGRTLH73 DDDSCQVIPV83 LPQVMMILIP93 GQTLPLQLFH 103 PQEVSMVRNL113 IQKDRTFAVL123 AYSNVQEREA133 QFGTTAEIYA143 YREEQDFGIE 153 IVKVKAIGRQ163 RFKVLELRTQ173 SDGIQQAKVQ183 ILPECVLPST193 MSAVQLESLN 203 KCQIFPCSYK222 WWQKYQKRKF232 HCANLTSWPR242 WLYSLYDAET252 LMDRIKKQLR 262 EWDENLKDDS272 LPSNPIDFSY282 RVAACLPIDD292 VLRIQLLKIG302 SAIQRLRCEL 312 DIMNKCTSLC322 CKQCQETEIT332 TKNEIFSLSL342 CGPMAAYVNP352 HGYVHETLTV 362 YKACNLNLIG372 RPSTEHSWFP382 GYAWTVAQCK392 ICASHIGWKF402 TATKKDMSPQ 412 KFWGLTRSAL422 LPTIP
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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 .RN3 or .RN32 or .RN33 or :3RN3;style chemicals stick;color identity;select .B:350 or .B:351 or .B:352 or .B:353 or .B:357 or .B:375 or .B:377 or .B:378 or .B:379 or .B:380 or .B:381 or .B:386 or .B:400 or .B:402; 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-(3-Chloro-4-Methylphenyl)-3-({2-[(3s)-2,6-Dioxopiperidin-3-Yl]-1-Oxo-2,3-Dihydro-1h-Isoindol-5-Yl}methyl)urea | Ligand Info | |||||
| Structure Description | Cereblon in complex with DDB1, CC-885, and GSPT1 | PDB:5HXB | ||||
| Method | X-ray diffraction | Resolution | 3.60 Å | Mutation | No | [6] |
| PDB Sequence |
NFDTSLPTSH
57 TYLGADMEEF67 HGRTLHDDDS77 CQVIPVLPQV87 MMILIPGQTL97 PLQLFHPQEV 107 SMVRNLIQKD117 RTFAVLAYSN127 VQEREAQFGT137 TAEIYAYREE147 QDFGIEIVKV 157 KAIGRQRFKV167 LELRTQSDGI177 QQAKVQILPE187 CVLPSTMSAV197 QLESLNKCQI 207 FPSKPVSYKW223 WQKYQKRKFH233 CANLTSWPRW243 LYSLYDAETL253 MDRIKKQLRE 263 WDENSLPSNP277 IDFSYRVAAC287 LPIDDVLRIQ297 LLKIGSAIQR307 LRCELDIMNK 317 CTSLCCKQCQ327 ETEITTKNEI337 FSLSLCGPMA347 AYVNPHGYVH357 ETLTVYKACN 367 LNLIGRPSTE377 HSWFPGYAWT387 VAQCKICASH397 IGWKFTATKK407 DMSPQKFWGL 417 TRSALLPTIP427 DTEDEVILCL442
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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 .85C or .85C2 or .85C3 or :385C;style chemicals stick;color identity;select .Z:150 or .Z:350 or .Z:351 or .Z:352 or .Z:353 or .Z:357 or .Z:377 or .Z:378 or .Z:379 or .Z:380 or .Z:381 or .Z:386 or .Z:400 or .Z:402; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-(4-chlorophenyl)-N-({2-[(3S)-2,6-dioxopiperidin-3-yl]-1-oxo-2,3-dihydro-1H-isoindol-5-yl}methyl)-2,2-difluoroacetamide | Ligand Info | |||||
| Structure Description | Cereblon in complex with DDB1, CC-90009, and GSPT1 | PDB:6XK9 | ||||
| Method | X-ray diffraction | Resolution | 3.64 Å | Mutation | No | [7] |
| PDB Sequence |
IINFDTSLPT
55 SHTYLGADME65 EFHGRTLHDD75 DSCQVIPVLP85 QVMMILIPGQ95 TLPLQLFHPQ 105 EVSMVRNLIQ115 KDRTFAVLAY125 SNVQEREAQF135 GTTAEIYAYR145 EEQDFGIEIV 155 KVKAIGRQRF165 KVLELRTQSD175 GIQQAKVQIL185 PECVLPSTMS195 AVQLESLNKC 205 QIFPSKPVSY221 KWWQKYQKRK231 FHCANLTSWP241 RWLYSLYDAE251 TLMDRIKKQL 261 REWDENLKDD271 SLPSNPIDFS281 YRVAACLPID291 DVLRIQLLKI301 GSAIQRLRCE 311 LDIMNKCTSL321 CCKQCQETEI331 TTKNEIFSLS341 LCGPMAAYVN351 PHGYVHETLT 361 VYKACNLNLI371 GRPSTEHSWF381 PGYAWTVAQC391 KICASHIGWK401 FTATKKDMSP 411 QKFWGLTRSA421 LLPTIPDVIL440 CL
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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 .V4M or .V4M2 or .V4M3 or :3V4M;style chemicals stick;color identity;select .Z:150 or .Z:350 or .Z:351 or .Z:352 or .Z:353 or .Z:357 or .Z:377 or .Z:378 or .Z:379 or .Z:380 or .Z:381 or .Z:386 or .Z:400 or .Z:402; 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-[3-[[1-[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]-2,5-bis(oxidanylidene)pyrrol-3-yl]amino]phenyl]-~{N}-(3-chloranyl-4-methyl-phenyl)propanamide | Ligand Info | |||||
| Structure Description | Crystal structure of DDB1-CRBN-ALV1 complex bound to Helios (IKZF2 ZF2) | PDB:7LPS | ||||
| Method | X-ray diffraction | Resolution | 3.78 Å | Mutation | No | [8] |
| PDB Sequence |
INFDTSLPTS
56 HTYLGADMEE66 FHGRTLHDDD76 SCQVIPVLPQ86 VMMILIPGQT96 LPLQLFHPQE 106 VSMVRNLIQK116 DRTFAVLAYS126 NVQEREAQFG136 TTAEIYAYRE146 EQDFGIEIVK 156 VKAIGRQRFK166 VLELRTQSDG176 IQQAKVQILP186 ECVLPSTMSA196 VQLESLNKCQ 206 IFPCSYKWWQ225 KYQKRKFHCA235 NLTSWPRWLY245 SLYDAETLMD255 RIKKQLREWD 265 ENLKDDSLPS275 NPIDFSYRVA285 ACLPIDDVLR295 IQLLKIGSAI305 QRLRCELDIM 315 NKCTSLCCKQ325 CQETEITTKN335 EIFSLSLCGP345 MAAYVNPHGY355 VHETLTVYKA 365 CNLNLIGRPS375 TEHSWFPGYA385 WTVAQCKICA395 SHIGWKFTAT405 KKDMSPQKFW 415 GLTRSALLPT425 IPDTEDEISP435 D
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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 .RN9 or .RN92 or .RN93 or :3RN9;style chemicals stick;color identity;select .B:100 or .B:102 or .B:152 or .B:350 or .B:351 or .B:352 or .B:353 or .B:377 or .B:378 or .B:379 or .B:380 or .B:381 or .B:386 or .B:400 or .B:402; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (-)-Thalidomide | Ligand Info | |||||
| Structure Description | Cereblon in complex with SALL4 and (S)-thalidomide | PDB:7BQU | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [9] |
| PDB Sequence |
CTSLCCKQCQ
327 ETEITTKNEI337 FSLSLCGPMA347 AYVNPHGYVH357 ETLTVYKASN367 LNLIGRPSTE 377 HSWFPGYAWT387 VAQCKICASH397 IGWKFTATKK407 DMSPQKFWGL417 TRSALLPTI |
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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 .EF2 or .EF22 or .EF23 or :3EF2;style chemicals stick;color identity;select .A:350 or .A:351 or .A:352 or .A:353 or .A:357 or .A:377 or .A:378 or .A:379 or .A:380 or .A:381 or .A:386 or .A:400 or .A:402; 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~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]-5-oxidanyl-isoindole-1,3-dione | Ligand Info | |||||
| Structure Description | Cereblon in complex with SALL4 and (S)-5-hydroxythalidomide | PDB:7BQV | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [9] |
| PDB Sequence |
CTSLCCKQCQ
327 ETEITTKNEI337 FSLSLCGPMA347 AYVNPHGYVH357 ETLTVYKASN367 LNLIGRPSTE 377 HSWFPGYAWT387 VAQCKICASH397 IGWKFTATKK407 DMSPQKFWGL417 TRSALLPTI |
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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 .F4U or .F4U2 or .F4U3 or :3F4U;style chemicals stick;color identity;select .A:350 or .A:351 or .A:352 or .A:353 or .A:357 or .A:377 or .A:378 or .A:379 or .A:380 or .A:381 or .A:386 or .A:400 or .A:402; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. J Med Chem. 2018 Jan 25;61(2):535-542. | ||||
| REF 2 | Molecular glue CELMoD compounds are regulators of cereblon conformation. Science. 2022 Nov 4;378(6619):549-553. | ||||
| REF 3 | Structural basis of lenalidomide-induced CK1Alpha degradation by the CRL4(CRBN) ubiquitin ligase. Nature. 2016 Apr 7;532(7597):127-30. | ||||
| REF 4 | Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science. 2018 Nov 2;362(6414):eaat0572. | ||||
| REF 5 | Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat Chem Biol. 2018 Jul;14(7):706-714. | ||||
| REF 6 | A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase. Nature. 2016 Jul 14;535(7611):252-7. | ||||
| REF 7 | CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells. Blood. 2021 Feb 4;137(5):661-677. | ||||
| REF 8 | Acute pharmacological degradation of Helios destabilizes regulatory T cells. Nat Chem Biol. 2021 Jun;17(6):711-717. | ||||
| REF 9 | Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide. Nat Commun. 2020 Sep 14;11(1):4578. | ||||
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