2021-2018 Publications

2021

 

109. Tarantelli, C., Cannas, E., Ekeh, H., Moscatello, C., Gaudio, E., Cascione, L., Napoli, S., Rech, C., Testa, A., Maniaci, C., Rinaldi, A., Zucca, E., Stathis, A., Ciulli, A., Bertoni, F.

The bromodomain and extra-terminal domain degrader MZ1 exhibits preclinical anti-tumoral activity in diffuse large B-cell lymphoma of the activated B cell-like type

Explor. Target Antitumor Ther. 2021, 2, 586–601

 

108. Klein, V.G., Bond, A.G., Craigon, C., Lokey, R.S.*, Ciulli, A.*

Amide-to-ester substitution as a strategy for optimizing PROTAC permeability and cellular activity

J. Med. Chem. 2021, 64 (24), 18082–18101

 

107. Müller, S., Ackloo, S., Al Chawaf, A., Al-Lazikani, B., Antolin, A., Baell, J.B., Beck, H., Beedie, S., Betz, U.A.K., Arruda Bezerra, G., Brennan, P.E., Brown, D., Brown, P.J., Bullock, A.N., Carter, A.J., Chaikuad, A., Chaineau, M., Ciulli, A., Collins, I., Dreher, J., Drewry, D., Edfeldt, K., Edwards, A.M., Egner, U., Frye, S.V., Fuchs, S.M., Hall, M.D., Hartung, I.V., Hillisch, A., Hitchcock, S.H., Homan, E., Kannan, N., Kiefer, J.R., Knapp, S., Kostic, M., Kubicek, S., Leach, A.R., Lindemann, S., Marsden, B.D., Matsui, H., Meier, J.L., Merk, D., Michel, M., Morgan, M.R., Mueller-Fahrnow, A., Owen, D.R., Perry, B.G., Rosenberg, S.H., Singh Saikatendu, K., Schapira, M., Scholten, C., Sharma, S., Simeonov, A., Sundström, M., Superti-Furga, G., Todd, M.H., Tredup, C., Vedadi, M., von Delft, F., Willson, T.M., Winter, G.E., Workman, P., Arrowsmith, C.H.

Target 2035 – update on the quest for a probe for every protein

RSC Med. Chem. 2022, 13, 13-21

 

106. Laveglia, V., Giachetti, A., Cerofolini, L., Haubrich, K., Fragai, M., Ciulli, A., Rosato, A.

Automated Determination of Nuclear Magnetic Resonance Chemical Shift Perturbations in Ligand Screening Experiments: The PICASSO Web Server

J. Chem. Inf. Model. 2021, 61 (12), 5726–5733

 

105. Imaide, S., Riching, K.M., Makukhin, N., Vetma, V., Whitworth, C., Hughes, S.J., Trainor, N., Mahan, S.D., Murphy, N., Cowan, A.D., Chan, K.-H., Craigon, C., Testa, A., Maniaci, C., Urh, M., Daniels, D.L.*; Ciulli, A.*

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Nat. Chem. Biol. 2021, 17 (11), 1157–1167

 

104. Riching, K.M., Vasta, J.D., Hughes, S.J., Zoppi, V., Maniaci, C., Testa, A., Urh, M., Ciulli, A.*, Daniels, D.L.*

Translating PROTAC chemical series optimization into functional outcomes underlying BRD7 and BRD9 protein degradation

Curr. Res. Chem. Biol., 2021, 1, 100009

 

103. Bond, A.G., Craigon, C., Chan, K.-H., Testa, A., Karapetsas, A., Fasimoye, R., Macartney, T., Blow, J.J., Alessi, D.R., Ciulli, A.*

Development of BromoTag: A “Bump-and-Hole”–PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins

J. Med. Chem. 2021, 64 (20), 15477–15502

  • PMID: 34652918 PMCID: PMC8558867
  • See Figures here
  • Featured in UoD and SLS News websites
  • Listed amongst the Most Read Articles in the journal (1-month timeframe, November 2021)
  • Highlighted in SynFacts
  • Our BromoTag-specific bumped-PROTAC degrader AGB1 is available from Tocris (April 2022)
  • The non-degrading epimer cis-AGB1 is also available from Tocris (April 2022)
  • A second BromoTag-specific bumped-PROTAC degrader AGB3 is also available from Tocris (November 2022)
  • Addition/Correction published (Web): January 22, 2025. DOI: 10.1021/acs.jmedchem.5c00108

 

102. Castro, G.V, Ciulli, A.*

Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay

RSC Med. Chem. 2021, 12, 1765-1770

 

(100. & 101. Casement et al. and Bartoschik et al. book chapters)

 

99. Ciulli, A.*, Trainor, N.

A beginner’s guide to PROTACs and targeted protein degradation

Biochem (Lond) 2021, 43 (5), 74–79

 

98. Frost, J.; Rocha, S.*; Ciulli, A.*

Von Hippel-Lindau (VHL) small molecule inhibitor binding increases stability and intracellular levels of VHL protein

J. Biol. Chem. 2021, 297 (2), 100910

 

97. Ciulli, A.; Hamann, L.; Jahnke, W.; Kalgutkar, A.S.; Magauer, T.; Ritter, T.; Steadman, V.; Williams, S.D.; Winter, G.; Hoegenauer, K.; Krawinkler, K.H.; Stepan, A.F.

The 2nd Alpine Winter Conference on Medicinal and Synthetic Chemistry.

ChemMedChem 2021, 16 (15), 2417-2413

 

96. Ciulli, A.*; Wertz, I.E.*

Editorial overview: Hot targets and new modalities.

Curr. Opin. Chem. Biol. 2021, 62, A1-A3

 

95. Pietrobono, S.; Gaudio, E.; Gagliardi, S.; Zitani, M.; Carrassa, L.; Migliorini, F.; Petricci, E.; Manetti, F.; Makukhin, N.; Bond, A.G.; Paradise, B.D.; Ciulli, A.; Fernandez-Zapico, M.E.; Bertoni, F.; Stecca, B.

Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma

Oncogene 2021, 40, 3799-3814

 

94. Farnaby, W.; Koegl, M.; McConnell, D.B.; Ciulli, A.

Transforming targeted cancer therapy with PROTACs: A forward-looking perspective

Curr. Opin. Pharmacol. 2021, 57, 175-183

 

93. Ramachandran, S.; Ciulli, A.*

Building ubiquitination machineries: E3 ligase multi-subunit assembly and substrate targeting by PROTACs and molecular glues

Curr. Opin. Struct. Biol. 2021, 67, 110-119

 

92. Ishida, T., Ciulli, A.*

E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones

SLAS Discov. 2021, 26 (4), 484-502

 

91. Makukhin, N., Ciulli, A.*

Recent advances in synthetic and medicinal chemistry of phosphotyrosine and phosphonate- based phosphotyrosine analogues

RSC Med. Chem. 2021, 12, 8-23

2020

 

90. Klein, V.G., Townsend, C.E., Testa, A., Zengerle, M., Maniaci, C., Hughes, S.J., Chan, K.-H., Ciulli, A., Lokey, R.S.

Understanding and improving the membrane permeability of VH032-based PROTACs

ACS Med. Chem. Lett. 2020, 11 (9), 1732-1738

 

89. Bond, A.G., Testa, A., Ciulli, A.*

Stereoselective Synthesis of Allele-Specific BET Inhibitors

Org. Biomol. Chem. 2020, 18, 7533-7539

 

88. Cipriano, A., Sbardella, G.,* Ciulli, A.*

Targeting epigenetic reader domains by chemical biology

Curr. Opin. Chem. Biol. 2020, 57, 82-94

  • PMID: 32739717
  • Read the article open access before September 18, 2020 via the Share Link here
  • See Figures here

 

87. Whitworth, C., Ciulli, A.*

Protein degraders extend their reach

Nature 2020, 584, 193-194

 

86. Simpson, L.M., Macartney, T.J., Nardin, A., Fulcher, L.J., Röth, S., Testa, A., Maniaci, C., Ciulli, A., Ganley, I.G., Sapkota, G.P.

Inducible Degradation of Target Proteins through a Tractable Affinity-Directed Protein Missile System

Cell Chem. Biol. 2020, 27 (9), 1164-1180.e5

 

85. Testa, A., Hughes, S.J.,  Lucas, X., Wright, J.E., Ciulli, A.*

Structure-Based Design of a Macrocyclic PROTAC

Angew. Chem. Int. Ed. 2020, 59, 1727-1734

  • PMID: 31746102 PMCID: PMC7004083
  • Pre-print posted at ChemRxiv on 22 July 2019; DOI: 10.26434/chemrxiv.8967941.v1
  • Selected as a “Hot paper” by the Editors of Angew. Chem. and Angew. Chem. Int. Ed.
  • See Figures here
  • The coordinates and structure factors of the associated co-crystal structure of the ternary complex between VHL, Brd4-BD2 and macroPROTAC-1 is available in the PDB with accession code 6SIS.
  • Listed amongst the Most Accessed in the journal for the period 02/2020 to 01/2021 (April 2021)

 

(84. Zollman & Ciulli book chapter)

 

83. Hassell-Hart, S., Runcie, A.C., Krojer, T., Doyle, J., Lineham, E., Ocasio, C.A., Neto, B.A.D., Fedorov, O., Marsh, G., Maple, H., Felix, R., Banks, R., Ciulli, A., Picaud, S., Filippakopoulos, P., von Delft, F., Brennan, P., Stewart, H.J.S., Chevassut, T.J., Walker, M., Austin, C., Morley, S., Spencer, J.

Synthesis and Biological Investigation of (+)-JD1, an Organometallic BET Bromodomain Inhibitor

Organometallics 2020, 39 (3), 408-416

2019

 

82. Tovell, H., Testa, A., Zhou, H., Shpiro, N., Crafter, C., Ciulli, A.*, Alessi, D.R.*

Design and characterization of SGK3-PROTAC1, an isoform specific SGK3 kinase PROTAC degrader

ACS Chem. Biol. 2019, 14 (9), 2024-2034

 

81. Maniaci, C., Ciulli, A.*

Bifunctional chemical probes inducing protein-protein interactions

Curr. Opin. Chem. Biol. 2019, 52, 145-156

  • Read the article open access until 2nd October 2019 via the Share Link here
  • See Figures here
  • Ranked amongst Most Popular Articles in the journal

 

80. Ciulli, A.*, Farnaby, W.*

Protein degradation for drug discovery. [Editorial]

Drug Discov. Today Technol. 2019 Apr 31: 1-3

 

79. Farnaby W, Koegl M, Roy MJ, Whitworth C, Diers E, Trainor N, Zollman D, Steurer S, Karolyi-Oezguer J, Riedmueller C, Gmaschitz T, Wachter J, Dank C, Galant M, Sharps B, Rumpel K, Traxler E, Gerstberger T, Schnitzer R, Petermann O, Greb P, Weinstabl H, Bader G, Zoephel A, Weiss-Puxbaum A, Ehrenhöfer-Wölfer K, Wöhrle S, Boehmelt G, Rinnenthal J, Arnhof H, Wiechens N, Wu MY, Owen-Hughes T, Ettmayer P, Pearson M, McConnell DB*, Ciulli A.*

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

Nat. Chem. Biol. 2019, 15 (7), 672-680

  • A Publisher Correction to this article was published on 02 July 2019
  • Featured in UoD and SLS News websites
  • Highlighted in EurekAlert, the Medical News, and mentioned by BioWorld
  • Read the article Open Access as SharedIt version here
  • See Figures here
  • The coordinates and structure factors of our co-crystal structures are available in the PDB. Accession codes of ternary complexes VCB (pVHL:ElonginC:ElonginB complex):PROTAC1:SMARCA2 bromodomain (PDB 6HAY), VCB:PROTAC2:SMARCA2 bromodomain (PDB 6HAX), and VCB:PROTAC2:SMARCA4 bromodomain (PDB 6HR2), as well as a binary complex between SMARCA2 bromodomain and SMARCA-BD ligand (PDB 6HAZ)
  • Featured in a News & Views article by Daffyd Owen in Nature Chemical Biology
  • Featured in Biocentury Innovation
  • Highlighted in SynFacts
  • Check out Darryl McConnell’s video on Structure-Based SMARCA2 PROTAC Design here.
  • Our SMARCA2/4 degrader ACBI1 (and cis-ACBI1) are available from Boehringer Ingelheim’s OpnMe Portal: order for free, no strings attached! (Update July 2021: in vivo DMPK data are now available online)
  • Our VHL ligand “VH101, phenol” functionalized for PROTAC conjugation is available from Tocris (January 2020)
  • Find out more about ACBI1 in the Chemical Probes Portal

 

78. Kung, W.-W., Ramachandran, S., Makukhin, N., Bruno, E., Ciulli, A.*

Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase

Nat. Commun. 2019, 10, 2534

  • Pre-print posted at bioRxiv 470187; 14 November 2018 doi: https://doi.org/10.1101/470187
  • See Figures here
  • Featured in SLS News
  • Read the SharedIt version here
  • The coordinates and structure factors of our co-crystal structures are available in the PDB. Accession codes of SOCS2:ElonginC:ElonginB in complex with EpoR (PDB 6I4X) and GHR peptides (PDBs 6I5J and 6I5N)

 

77. Tovell, H., Testa, A., Maniaci, C., Zhou, H., Prescott, A.R., Macartney, T., Ciulli, A.*, Alessi, D.R.*

Rapid and reversible knockdown of endogenously tagged endosomal proteins via an optimized HaloPROTAC degrader

ACS Chem. Biol. 2019, 14 (5), 882-892

 

76. Girardini, M., Maniaci, C., Hughes, S.J., Testa, A., Ciulli, A.*

Cereblon vs VHL: Hijacking E3 Ligases Against Each Other Using PROTACs

Bioorg. Med. Chem. 2019, 27 (12), 2466-2479

 

75. Popow, J., Arnhof, H., Bader, G., Berger, H., Ciulli, A., Covini, D., Dank, C., Gmaschitz, T., Greb, P., Karolyi-Özguer, J., Koegl, M., McConnell, D.B., Pearson, M., Rieger, M., Rinnenthal, J., Roessler, V., Schrenk, A., Spina, M., Steurer, S., Trainor, N., Traxler, E., Wieshofer, C., Zoephel, A., Ettmayer, P.

Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

J. Med. Chem. 2019, 62 (5), 2508-2520

  • PTK2 PROTACs BI-0319 (VHL-based) and BI-3663 (CRBN-based) are available for free from the OpnMe Portal.

 

74. Roy, M.J., Winkler, S., Hughes, S.J., Whitworth, C., Galant, M., Farnaby, W., Rumpel, K., Ciulli, A.*

SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate

ACS Chem. Biol. 2019, 14 (3), 361-368

 

73. Frost, J., Ciulli, A.*, Rocha, S.*

RNA-seq analysis of PHD and VHL inhibitors reveals differences and similarities to the hypoxia response. [version 1; referees: 2 approved]

Wellcome Open Res. 2019, 4:17 (https://doi.org/10.12688/wellcomeopenres.15044.1)

 

72. Castro, G.V, Ciulli, A.*

Spy vs. spy: selecting the best reporter for 19F NMR competition experiments

Chem. Commun. 2019, 55 (10), 1482-1485

 

71. Zoppi, V., Hughes, S.J., Maniaci, C., Testa, A., Gmaschitz, T., Wieshofer, C., Koegl, M., Riching, K., Daniels, D.L., Spallarossa, A., and Ciulli, A.*

Iterative design and optimization of initially inactive Proteolysis Targeting Chimeras (PROTACs) identify VZ185 as a potent, fast and selective von Hippel-Lindau (VHL)-based dual degrader probe of BRD9 and BRD7

J. Med. Chem. 2019, 62 (2), 699-726

  • See Figures here
  • The coordinates and structure factors of the associated co-crystal structure of human BRD9 bromodomain in complex with PROTAC 5 is available in the PDB with accession code 6HM0
  • Listed as 1st Most Read Article in the journal (1-month timeframe, Jan 2019)
  • Highlighted in the blog Promega Connection: “A Roadmap for PROTAC Development”
  • Find out more about VZ185 in the Chemical Probes Portal
  • Our dual Brd7/9 degrader VZ185 is available from Tocris (October 2019)
  • The inactive epimer cis-VZ185 is also available from Tocris (April 2020)
  • The PROTAC VZ185 (together with its negative control cis-VZ185) are also available from Boehringer Ingelheim’s OpnMe Portal: order for free, no strings attached!
  • Our VHL ligand “VH101, phenol” functionalized for PROTAC conjugation is available from Tocris (January 2020)

 

70. Aresu, L., Ferraresso, S., Marconato, L., Cascione, L., Napoli, S., Gaudio, E., Kwee, I., Tarantelli, C., Testa, A., Maniaci, C., Ciulli, A., Hillmann, P., Bohnacker, T., Wymann, M.P., Comazzi, S., Milan, M., Riondato, F., Dalla Rovere, G., Giantin, M., Giannuzzi, D., Bertoni, F.

New Molecular And Therapeutic Insights Into Canine Diffuse Large B Cell Lymphoma Elucidates The Role Of The Dog As A Model For Human Disease

Haematologica 2019, 104 (6), e256-e259

 

2018

 

69. Lucas, X., Van Molle, I., Ciulli, A.*

Surface probing by fragment-based screening and computational methods identifies ligandable pockets on the von Hippel-Lindau (VHL) E3 ubiquitin ligase

J. Med. Chem. 2018, 61 (16), 7387-7393

  • See Figures here
  • The coordinates and structure factors of our co-crystal structures are available in the PDB. Accession codes of VCB (pVHL:ElonginC:ElonginB complex) in complex with MB235 (PDB 6GMN), MB756 (PDB 6GMQ), MB1200 (PDB 6GMX), and VCBH (pVHL:ElonginC:ElonginB:HIF-1alpha complex) in complex with MB756 (PDB 6GMR)
  • Listed amongst the Most Read Articles in the journal (Aug 2018)
  • Highlighted in the Faculty of 1000 Prime Access the recommendation on F1000Prime

 

68. Testa, A., Lucas, X., Castro, G.V., Chan, K.-H., Wright, J.E., Runcie, A.C., Gadd, M.S., Harrison, W.T.A., Ko, E.-J., Fletcher, D., Ciulli, A.*

3-Fluoro-4-hydroxyprolines: Synthesis, conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation

J. Am. Chem. Soc. 2018, 140 (29), 9299-9313

  • See Figures here
  • The coordinates and structure factors of our co-crystal structures are available in the PDB, with accession codes: 6GFX, 6GFY and 6GFZ
  • Addition/Correction published (Web): April 24, 2019. DOI: 10.1021/jacs.9b03833

 

67. Soares, P., Lucas, X., Ciulli, A.*

Thioamide substitution to probe the hydroxyproline recognition of VHL ligands

Bioorg. Med. Chem. 2018, 26 (11), 2992-2995

  • See Figures here
  • The article is a contribution to the journal’s Special Issue for the 2018 Tetrahedron Young Investigators Award for Matthew Fuchter
  • The coordinates and structure factors of our co-crystal structures are available in the Protein DataBank, with accession codes: 6FMI, 6FMJ, and 6FMK
  • 4th Most Downloaded Article in the journal (June 2018)

 

66. Amato, A., Lucas, X., Bortoluzzi, A., Wright, D., Ciulli, A.*

Targeting ligandable pockets on plant homeodomain (PHD) zinc finger domains by a fragment-based approach

ACS Chem. Biol. 2018, 13 (4), 915-921

  • See Figures here
  • The coordinates and structure factors of our co-crystal structures are available in the Protein DataBank, with accession codes: 6FHU, 6FKP, 6FI0, 6FAP, 6FHQ, and 6FI1

 

65. Runcie, A.C., Zengerle, M., Chan, K.-H., Testa, A., van Beurden, L., Baud, M.G.J., Epemolu, O., Ellis, L.C.J., Read, K.D., Coulthard, V., Brien, A. and Ciulli, A.*

Optimization of a “bump-and-hole” approach to allele-selective BET bromodomain inhibition

Chem. Sci. 2018, 9, 2452-2468

  • See Figures here
  • The coordinates and structure factors of our co-crystal structures are available in the Protein DataBank, with accession codes: 5O39, 5O3A, 5O3B, 5O3C, 5O3D, 5O3E, 5O3F, 5O3G, 5O3H and 5O3I