7Z76
 
 | | Crystal structure of compound 10 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB | | Descriptor: | (2~{S},4~{R})-~{N}-[(1~{R})-2-[(2~{R})-1-[4-(4-bromanyl-7-cyclopentyl-5-oxidanylidene-benzimidazolo[1,2-a]quinazolin-9-yl)piperidin-1-yl]propan-2-yl]oxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-1-[(2~{S})-2-[[1-(dimethylamino)cyclopropyl]carbonylamino]-3,3-dimethyl-butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, Elongin-B, Elongin-C, ... | | Authors: | Bader, G, Boettcher, J, Wolkerstorfer, B. | | Deposit date: | 2022-03-15 | | Release date: | 2022-09-14 | | Last modified: | 2024-01-31 | | Method: | X-RAY DIFFRACTION (1.32 Å) | | Cite: | A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo.
Nat Commun, 13, 2022
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7JTO
 | | Crystal structure of Protac MS33 in complex with the WD repeat-containing protein 5 and pVHL:ElonginC:ElonginB | | Descriptor: | 1,2-ETHANEDIOL, 3-methyl-N-(11-{[2-(4-{[4'-(4-methylpiperazin-1-yl)-3'-{[6-oxo-4-(trifluoromethyl)-5,6-dihydropyridine-3-carbonyl]amino}[1,1'-biphenyl]-3-yl]methyl}piperazin-1-yl)ethyl]amino}-11-oxoundecanoyl)-L-valyl-(4R)-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}-L-prolinamide, Elongin-B, ... | | Authors: | Kottur, J, Jain, R, Aggarwal, A.K. | | Deposit date: | 2020-08-18 | | Release date: | 2021-10-06 | | Last modified: | 2023-10-18 | | Method: | X-RAY DIFFRACTION (1.7 Å) | | Cite: | A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models.
Sci Transl Med, 13, 2021
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8BDS
 | | Ternary complex between VCB, BRD4-BD1 and PROTAC 48 | | Descriptor: | (2S,4R)-N-[(1S)-1-(4-chlorophenyl)-3-[2-[2-[2-[2-[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8$l^{5},11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-9-yl]ethanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-3-oxidanylidene-propyl]-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, 1,2-ETHANEDIOL, Bromodomain-containing protein 4, ... | | Authors: | Sorrell, F.J, Mueller, J.E, Lehmann, M, Wegener, A. | | Deposit date: | 2022-10-20 | | Release date: | 2023-02-15 | | Last modified: | 2024-02-07 | | Method: | X-RAY DIFFRACTION (1.72 Å) | | Cite: | Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.
Chemmedchem, 18, 2023
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4AJY
 | | von Hippel-Lindau protein-ElonginB-ElonginC complex, bound to Hif1- alpha peptide | | Descriptor: | GLYCEROL, HYPOXIA-INDUCIBLE FACTOR 1-ALPHA, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, ... | | Authors: | Van Molle, I, Thomann, A, Buckley, D.L, So, E.C, Lang, S, Crews, C.M, Ciulli, A. | | Deposit date: | 2012-02-21 | | Release date: | 2012-11-14 | | Last modified: | 2023-12-20 | | Method: | X-RAY DIFFRACTION (1.73 Å) | | Cite: | Dissecting Fragment-Based Lead Discovery at the Von Hippel-Lindau Protein:Hypoxia Inducible Factor 1Alpha Protein-Protein Interface.
Chem.Biol., 19, 2012
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6GMR
 | | pVHL:EloB:EloC in complex with (4-(1H-pyrrol-1-yl)phenyl)methanol | | Descriptor: | (4-pyrrol-1-ylphenyl)methanol, Elongin-B, Elongin-C, ... | | Authors: | Van Molle, I, Lucas, X, Ciulli, A. | | Deposit date: | 2018-05-28 | | Release date: | 2018-08-08 | | Last modified: | 2018-09-05 | | Method: | X-RAY DIFFRACTION (1.75 Å) | | Cite: | Surface Probing by Fragment-Based Screening and Computational Methods Identifies Ligandable Pockets on the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.
J. Med. Chem., 61, 2018
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6HR2
 | | Crystal structure of PROTAC 2 in complex with the bromodomain of human SMARCA4 and pVHL:ElonginC:ElonginB | | Descriptor: | (2~{S},4~{R})-~{N}-[[2-[2-[4-[[4-[3-azanyl-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenyl]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2~{S})-2-[(1-fluoranylcyclopropyl)carbonylamino]-3,3-dimethyl-butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, 1,2-ETHANEDIOL, DIMETHYL SULFOXIDE, ... | | Authors: | Roy, M, Bader, G, Diers, E, Trainor, N, Farnaby, W, Ciulli, A. | | Deposit date: | 2018-09-26 | | Release date: | 2019-06-12 | | Last modified: | 2024-05-15 | | Method: | X-RAY DIFFRACTION (1.76 Å) | | Cite: | BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design.
Nat.Chem.Biol., 15, 2019
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6I7Q
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8BB3
 | | Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker (conformation #1) | | Descriptor: | 1,2-ETHANEDIOL, Elongin-B, Elongin-C, ... | | Authors: | Kraemer, A, Doelle, A, Knapp, S, Structural Genomics Consortium (SGC) | | Deposit date: | 2022-10-12 | | Release date: | 2022-11-09 | | Last modified: | 2024-01-31 | | Method: | X-RAY DIFFRACTION (1.8 Å) | | Cite: | Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker (conformation #1)
To Be Published
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6GFX
 | | pVHL:EloB:EloC in complex with modified HIF-1a CODD peptide containing (3R,4S)-3-fluoro-4-hydroxyproline (ligand 13a) | | Descriptor: | Elongin-B, Elongin-C, FLUORINATED HYPOXIA-INDUCIBLE FACTOR 1 ALPHA PEPTIDE, ... | | Authors: | Castro, G.V, Testa, A, Ciulli, A. | | Deposit date: | 2018-05-02 | | Release date: | 2018-07-11 | | Last modified: | 2018-08-01 | | Method: | X-RAY DIFFRACTION (1.83 Å) | | Cite: | 3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation.
J. Am. Chem. Soc., 140, 2018
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1LM8
 | | Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex | | Descriptor: | ELONGIN B, ELONGIN C, Hypoxia-inducible factor 1 alpha, ... | | Authors: | Min, J.-H, Yang, H, Ivan, M, Gertler, F, Kaelin JR, W.G, Pavletich, N.P. | | Deposit date: | 2002-04-30 | | Release date: | 2002-06-12 | | Last modified: | 2023-08-16 | | Method: | X-RAY DIFFRACTION (1.85 Å) | | Cite: | Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
Science, 296, 2002
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6ZHC
 | | PROTAC6 mediated complex of VHL:EloB:EloC and Bcl-xL | | Descriptor: | 1,2-ETHANEDIOL, 2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1~{H}-isoquinolin-2-yl]-5-[3-[4-[3-[2-[2-[2-[2-[2-[3-[[(2~{S})-3,3-dimethyl-1-[(2~{S},4~{R})-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]-4-oxidanyl-pyrrolidin-1-yl]-1-oxidanylidene-butan-2-yl]amino]-3-oxidanylidene-propoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]prop-1-ynyl]phenoxy]propyl]-1,3-thiazole-4-carboxylic acid, Bcl-2-like protein 1, ... | | Authors: | Chung, C. | | Deposit date: | 2020-06-22 | | Release date: | 2020-08-05 | | Last modified: | 2024-01-24 | | Method: | X-RAY DIFFRACTION (1.92 Å) | | Cite: | Structural Insights into PROTAC-Mediated Degradation of Bcl-xL.
Acs Chem.Biol., 15, 2020
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6GMN
 | | pVHL:EloB:EloC in complex with methyl 4H-furo[3,2-b]pyrrole-5-carboxylate | | Descriptor: | ACETATE ION, Elongin-B, Elongin-C, ... | | Authors: | Van Molle, I, Lucas, X, Ciulli, A. | | Deposit date: | 2018-05-27 | | Release date: | 2018-08-08 | | Last modified: | 2018-09-05 | | Method: | X-RAY DIFFRACTION (1.94 Å) | | Cite: | Surface Probing by Fragment-Based Screening and Computational Methods Identifies Ligandable Pockets on the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.
J. Med. Chem., 61, 2018
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6I7R
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7Z77
 | | Crystal structure of compound 6 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB | | Descriptor: | (2~{S},4~{R})-~{N}-[(1~{S})-4-[4-(4-bromanyl-7-cyclopentyl-5-oxidanylidene-benzimidazolo[1,2-a]quinazolin-9-yl)piperidin-1-yl]-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]butyl]-1-[(2~{S})-2-[(1-fluoranylcyclopropyl)carbonylamino]-3,3-dimethyl-butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, Elongin-B, Elongin-C, ... | | Authors: | Bader, G, Boettcher, J, Wolkerstorfer, B. | | Deposit date: | 2022-03-15 | | Release date: | 2022-09-14 | | Last modified: | 2024-01-31 | | Method: | X-RAY DIFFRACTION (1.97 Å) | | Cite: | A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo.
Nat Commun, 13, 2022
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8P0F
 | | Crystal structure of the VCB complex with compound 1. | | Descriptor: | (3~{R},5~{R})-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-5-oxidanyl-2-oxidanylidene-1-pyridin-2-yl-piperidine-3-carboxamide, CHLORIDE ION, Elongin-B, ... | | Authors: | Bader, G, Boettcher, J, Wolkerstorfer, B. | | Deposit date: | 2023-05-10 | | Release date: | 2023-05-31 | | Last modified: | 2023-12-20 | | Method: | X-RAY DIFFRACTION (1.98 Å) | | Cite: | Drugit: Crowd-sourcing molecular design of non-peptidic VHL binders
Chemrxiv, 2023
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9BOL
 | | Crystal structure of the complex between VHL, ElonginB, ElonginC, and compound 5 | | Descriptor: | (4R)-1-[(2S)-2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-3,3-dimethylbutanoyl]-4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}-L-prolinamide, 1,2-ETHANEDIOL, CHLORIDE ION, ... | | Authors: | Murray, J.M, Wu, H, Fuhrmann, J, Fairbrother, W.J, DiPasquale, A. | | Deposit date: | 2024-05-03 | | Release date: | 2024-05-29 | | Method: | X-RAY DIFFRACTION (1.99 Å) | | Cite: | Potency-enhanced peptidomimetic VHL ligands with improved oral bioavailability
To Be Published
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4B9K
 | | pVHL-ELOB-ELOC complex_(2S,4R)-1-(3-amino-2-methylbenzoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bound | | Descriptor: | (2S,4R)-1-(3-amino-2-methylbenzoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, ACETATE ION, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, ... | | Authors: | Buckley, D.L, Gustafson, J.L, VanMolle, I, Roth, A.G, SeopTae, H, Gareiss, P.C, Jorgensen, W.L, Ciulli, A, Crews, C.M. | | Deposit date: | 2012-09-05 | | Release date: | 2012-10-24 | | Last modified: | 2024-05-01 | | Method: | X-RAY DIFFRACTION (2 Å) | | Cite: | Small-Molecule Inhibitors of the Interaction between the E3 Ligase Vhl and Hif1 Alpha
Angew.Chem.Int.Ed.Engl., 51, 2012
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1LQB
 | | Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex | | Descriptor: | Elongin B, Elongin C, Hypoxia-inducible factor 1 ALPHA, ... | | Authors: | Hon, W.C, Wilson, M.I, Harlos, K, Claridge, T.D, Schofield, C.J, Pugh, C.W, Maxwell, P.H, Ratcliffe, P.J, Stuart, D.I, Jones, E.Y. | | Deposit date: | 2002-05-09 | | Release date: | 2002-07-03 | | Last modified: | 2023-08-16 | | Method: | X-RAY DIFFRACTION (2 Å) | | Cite: | Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL.
Nature, 417, 2002
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6BVB
 | | Crystal structure of HIF-2alpha-pVHL-elongin B-elongin C | | Descriptor: | Elongin-B, Elongin-C, Hypoxia-Inducible Factor 2 alpha, ... | | Authors: | Tarade, D, Ohh, M, Lee, J.E. | | Deposit date: | 2017-12-12 | | Release date: | 2018-08-01 | | Last modified: | 2023-10-04 | | Method: | X-RAY DIFFRACTION (2.002 Å) | | Cite: | HIF-2 alpha-pVHL complex reveals broad genotype-phenotype correlations in HIF-2 alpha-driven disease.
Nat Commun, 9, 2018
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8BDJ
 | | VCB in complex with compound 30 | | Descriptor: | (2~{S},4~{R})-~{N}-[(1~{S})-1-[4-chloranyl-2-(2-methoxyethoxy)phenyl]ethyl]-1-[(2~{R})-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, Elongin-B, Elongin-C, ... | | Authors: | Sorrell, F.J, Mueller, J.E, Lehmann, M, Wegener, A. | | Deposit date: | 2022-10-19 | | Release date: | 2023-02-15 | | Last modified: | 2024-02-07 | | Method: | X-RAY DIFFRACTION (2.02 Å) | | Cite: | Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.
Chemmedchem, 18, 2023
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8BDM
 | | VCB in complex with compound 26 | | Descriptor: | (2~{S},4~{R})-~{N}-[[2-(2-methoxyethoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2~{R})-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide, Elongin-B, Elongin-C, ... | | Authors: | Sorrell, F.J, Mueller, J.E, Lehmann, M, Wegener, A. | | Deposit date: | 2022-10-19 | | Release date: | 2023-02-15 | | Last modified: | 2024-02-07 | | Method: | X-RAY DIFFRACTION (2.021 Å) | | Cite: | Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.
Chemmedchem, 18, 2023
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8BB2
 | | Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker (conformation #2) | | Descriptor: | 1,2-ETHANEDIOL, Elongin-B, Elongin-C, ... | | Authors: | Kraemer, A, Doelle, A, Knapp, S, Structural Genomics Consortium (SGC) | | Deposit date: | 2022-10-12 | | Release date: | 2022-11-09 | | Last modified: | 2024-01-31 | | Method: | X-RAY DIFFRACTION (2.05 Å) | | Cite: | Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker (conformation #2)
To Be Published
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4W9H
 | | pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-acetamido-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 7) | | Descriptor: | N-acetyl-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide, Transcription elongation factor B polypeptide 1, Transcription elongation factor B polypeptide 2, ... | | Authors: | Gadd, M.S, Soares, P, Galdeano, C, van Molle, I, Ciulli, A. | | Deposit date: | 2014-08-27 | | Release date: | 2014-09-10 | | Last modified: | 2024-01-10 | | Method: | X-RAY DIFFRACTION (2.1 Å) | | Cite: | Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities.
J.Med.Chem., 57, 2014
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4W9F
 | | pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 5) | | Descriptor: | (4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide, Transcription elongation factor B polypeptide 1, Transcription elongation factor B polypeptide 2, ... | | Authors: | van Molle, I, Hewitt, S, Galdeano, C, Gadd, M.S, Ciulli, A. | | Deposit date: | 2014-08-27 | | Release date: | 2014-09-10 | | Last modified: | 2024-01-10 | | Method: | X-RAY DIFFRACTION (2.1 Å) | | Cite: | Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities.
J.Med.Chem., 57, 2014
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5NVV
 | | pVHL:EloB:EloC in complex with (2S,4R)-4-hydroxy-1-((S)-2-(2-hydroxyacetamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 3) | | Descriptor: | (2~{S},4~{R})-1-[(2~{S})-3,3-dimethyl-2-(2-oxidanylethanoylamino)butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide, Elongin-B, Elongin-C, ... | | Authors: | Gadd, M.S, Soares, P, Galdeano, C, Ciulli, A. | | Deposit date: | 2017-05-04 | | Release date: | 2017-09-20 | | Last modified: | 2024-01-17 | | Method: | X-RAY DIFFRACTION (2.1 Å) | | Cite: | Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298).
J. Med. Chem., 61, 2018
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