Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T15894
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| Target Name |
Cerebron E3 ubiquitin ligase complex (CRL4-CRBN E3 ubiquitin ligase)
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| Gene Name |
CUL4A/CUL4B-DDB1-CRBN
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Lupus erythematosus [ICD-11: 4A40] | |||||
| 2 | Prostate cancer [ICD-11: 2C82] | |||||
| UniProt ID | ||||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | KPG-121 | Drug Info | Phase 1 | Prostate cancer | [2] | |
| 2 | KPG-818 | Drug Info | Phase 1 | Systemic lupus erythematosus | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | KPG-121 | Drug Info | [1] | |||
| 2 | KPG-818 | Drug Info | [1] | |||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Cystein-S-Yl Cacodylate | Ligand Info | |||||
| Structure Description | Structure of the DDB1-CRBN E3 ubiquitin ligase bound to thalidomide | PDB:4CI1 | ||||
| Method | X-ray diffraction | Resolution | 2.98 Å | Mutation | No | [4] |
| PDB Sequence |
SYNYVVTAQK
11 PTAVNGCVTG21 HFTSAEDLNL31 LIAKNTRLEI41 YVVTAEGLRP51 VKEVGMYGKI 61 AVMELFRPKG71 ESKDLLFILT81 AKYNAILEYK92 QSGESIDIIT102 RAHGNVQDRI 112 GRPSETGIIG122 IIDPECRMIG132 LRLYDGLFKV142 IPLKELKAFN156 IRLEELHVID 166 VKFLYGCQAP176 TICFVYQDPQ186 GRHVKTYEVS196 LREKEFNKGP206 WKQENVEAEA 216 SMVIAVPEPF226 GGAIIIGQES236 ITYHNGDKYL246 AIAPPIIKQS256 TIVCHNRVDP 266 NGSRYLLGDM276 EGRLFMLLLL300 RVELLGETSI310 AECLTYLDNG320 VVFVGSRLGD 330 SQLVKLNVDS340 NEQGSYVVAM350 ETFTNLGPIV360 DMCVVDLERQ370 GQGQLVTCSG 380 AFKEGSLRII390 RNGIGIHEHA400 SIDLPGIKGL410 WPLRSDPNRE420 TDDTLVLSFV 430 GQTRVLMLNG440 EEVEETELMG450 FVDDQQTFFC460 GNVAHQQLIQ470 ITSASVRLVS 480 QEPKALVSEW490 KEPQAKNISV500 ASCNSSQVVV510 AVGRALYYLQ520 IHPQELRQIS 530 HTEMEHEVAC540 LDITPLGDSN550 GLSPLCAIGL560 WTDISARILK570 LPSFELLHKE 580 MLGGEIIPRS590 ILMTTFESSH600 YLLCALGDGA610 LFYFGLNIET620 GLLSDRKKVT 630 LGTQPTVLRT640 FRSLSTTNVF650 ACSDRPTVIY660 SSNHKLVFSN670 VNLKEVNYMC 680 PLNSDGYPDS690 LALANNSTLT700 IGTIDEIQKL710 HIRTVPLYES720 PRKICYQEVS 730 QCFGVLSSRI740 EVQDTSGGTT750 ALRPSASTQA760 LSSSVSSSKL770 FEEVEVHNLL 792 IIDQHTFEVL802 HAHQFLQNEY812 ALSLVSCKLG822 KDPNTYFIVG832 TAMVYPEEAE 842 PKQGRIVVFQ852 YSDGKLQTVA862 EKEVKGAVYS872 MVEFNGKLLA882 SINSTVRLYE 892 WTTEKELRTE902 CNHYNNIMAL912 YLKTKGDFIL922 VGDLMRSVLL932 LAYKPMEGNF 942 EEIARDFNPN952 WMSAVEILDD962 DNFLGAENAF972 NLFVQKTTDE987 ERQHLQEVGL 997 FHLGEFVNVF1007 CHGSLVMTPT1024 QGSVLFGTVN1034 GMIGLVTSLS1044 ESWYNLLLDM 1054 QNRLNKVIKS1064 VGKIEHSFWR1074 SFHTERKTEP1084 ATGFIDGDLI1094 ESFLDISRPK 1104 MQEVVANLQK1121 REATADDLIK1131 VVEELTRIH
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MET57
3.269
LEU77
3.525
PHE78
3.381
ILE79
3.056
LEU80
4.143
THR81
3.557
ASN85
3.176
ALA86
1.347
ILE88
1.350
LEU89
3.970
THR102
4.431
ALA104
3.179
HIS105
4.144
LEU152
3.701
ARG928
3.425
VAL930
4.067
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| Ligand Name: (2R)-2-({9-(1-methylethyl)-6-[(4-pyridin-2-ylbenzyl)amino]-9H-purin-2-yl}amino)butan-1-ol | Ligand Info | |||||
| Structure Description | Structure of DDB1 bound to CR8-engaged CDK12-cyclinK | PDB:6TD3 | ||||
| Method | X-ray diffraction | Resolution | 3.46 Å | Mutation | Yes | [5] |
| PDB Sequence |
MSYNYVVTAQ
10 KPTAVNGCVT20 GHFTSAEDLN30 LLIAKNTRLE40 IYVVTAEGLR50 PVKEVGMYGK 60 IAVMELFRPK70 GESKDLLFIL80 TAKYNACILE90 YKQSGESIDI100 ITRAHGNVQD 110 RIGRPSETGI120 IGIIDPECRM130 IGLRLYDGLF140 KVIPLDRDNK150 ELKAFNIRLE 160 ELHVIDVKFL170 YGCQAPTICF180 VYQDPQGRHV190 KTYEVSLREK200 EFNKGPWKQE 210 NVEAEASMVI220 AVPEPFGGAI230 IIGQESITYH240 NGDKYLAIAP250 PIIKQSTIVC 260 HNRVDPNGSR270 YLLGDMEGRL280 FMLLLEKEEQ290 MDGTVTLKDL300 RVELLGETSI 310 AECLTYLDNG320 VVFVGSRLGD330 SQLVKLNVDS340 NEQGSYVVAM350 ETFTNLGPIV 360 DMCVVDLERQ370 GQGQLVTCSG380 AFKEGSLRII390 RNGQKLHIRT714 VPLYESPRKI 724 CYQEVSQCFG734 VLSSRIEVQD744 TSGGTTALRP754 SASTQALSSS764 VSSSKLFSSS 774 TAPHETSFGE784 EVEVHNLLII794 DQHTFEVLHA804 HQFLQNEYAL814 SLVSCKLGKD 824 PNTYFIVGTA834 MVYPEEAEPK844 QGRIVVFQYS854 DGKLQTVAEK864 EVKGAVYSMV 874 EFNGKLLASI884 NSTVRLYEWT894 TEKELRTECN904 HYNNIMALYL914 KTKGDFILVG 924 DLMRSVLLLA934 YKPMEGNFEE944 IARDFNPNWM954 SAVEILDDDN964 FLGAENAFNL 974 FVCQKDSAAT984 TDEERQHLQE994 VGLFHLGEFV1004 NVFCHGSLVM1014 QNLGETSTPT 1024 QGSVLFGTVN1034 GMIGLVTSLS1044 ESWYNLLLDM1054 QNRLNKVIKS1064 VGKIEHSFWR 1074 SFHTERKTEP1084 ATGFIDGDLI1094 ESFLDISRPK1104 MQEVVANLQY1114 DDGSGMKREA 1124 TADDLIKVVE1134 ELTRIH
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Clinical pipeline report, company report or official report of Kangpu Biopharmaceuticals. | |||||
| REF 2 | ClinicalTrials.gov (NCT03569280) Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT04643067) A Study to Assess the Safety and Tolerability, PK and Efficacy of KPG-818 in Mild to Moderate SLE Patients (Lupus). U.S. National Institutes of Health. | |||||
| REF 4 | Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014 Aug 7;512(7512):49-53. | |||||
| REF 5 | The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K. Nature. 2020 Sep;585(7824):293-297. | |||||
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