Publications

18. Targeting cancer with small molecule pan-KRAS degraders

Johannes Popow*, William Farnaby*, Andreas Gollner*, Christiane Kofink*, Gerhard Fischer, Melanie Wurm, David Zollman, Andre Wijaya, Nikolai Mischerikow, Carina Hasenoehrl, Polina Prokofeva, Heribert Arnhof, Silvia Arce-Solano, Sammy Bell, Georg Boeck, Emelyne Diers, Aileen B Frost, Jake Goodwin-Tindall, Jale Karolyi-Oezguer, Shakil Khan, Theresa Klawatsch, Manfred Koegl, Roland Kousek, Barbara Kratochvil, Katrin Kropatsch, Arnel A Lauber, Ross McLennan, Sabine Olt, Daniel Peter, Oliver Petermann, Vanessa Roessler, Peggy Stolt-Bergner, Patrick Strack, Eva Strauss, Nicole Trainor, Vesna Vetma, Claire Whitworth, Siying Zhong, Jens Quant, Harald Weinstabl, Bernhard Küster, Peter Ettmayer (lead/corresponding author), Alessio Ciulli (lead/corresponding author)

*contributed equally as first author

Science. Publication Date: September 19, 2024, doi: 10.1126/science.adm8684

Pre-print first posted at bioRxiv on 26th October 2023; doi: 10.1101/2023.10.24.563163

17. Confounding factors in targeted degradation of short-lived proteins

Vesna Vetma, Laura Casares-Perez, Ján Eliaš, Andrea Stingu, Anju Kombara, Teresa Gmaschitz, Nina Braun, Tuncay Ciftci, Georg Dahmann, Emelyne Diers, Thomas Gerstberger, Peter Greb, Giorgia Kidd, Christiane Kofink, Ilaria Puoti, Valentina Spiteri, Nicole Trainor, Yvonne Westermaier, Claire Whitworth, Alessio Ciulli, William Farnaby, Kirsten McAulauy, Aileen B. Frost, Nicola Chessum, Manfred Koegl

ACS Chem. Biol. Publication Date: July 3, 2024, doi: 10.1021/acschembio.4c00152

Pre-print first posted at BioRxiv on 22 February 2024; doi: 10.1101/2024.02.19.581012

16. Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders

Alena Kroupova, Valentina A. Spiteri, Hirotake Furihata, Darren Darren, Sarath Ramachandran, Zoe J. Rutter, Sohini Chakraborti, Kevin Haubrich, Julie Pethe, Denzel Gonzales, Andre Wijaya, Maria Rodriguez-Rios, Dylan M. Lynch, William Farnaby, Mark A. Nakasone, *David Zollman, *Alessio Ciulli

*co-corresponding authors

bioRxiv 2024.01.17 doi: 10.1101/2024.01.17.575503

15. Breaking free from the crystal lattice: Structural biology in solution to study protein degraders.

Kevin Haubrich, Valentina Spiteri, William Farnaby, Frank Sobott, Alessio Ciulli

Curr Opin Struct Biol 2023, 79, 10234.

doi: 10.1016/j.sbi.2023.102534

14. Crystallization of VHL-based PROTAC-induced ternary complexes

Andre J. Wijaya, William Farnaby, Alessio Ciulli

Methods Enzymol 2023, 681, 242-261.

doi: 10.1016/bs.mie.2022.10.005

13. A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo

Christiane Kofink, Nicole Trainor, Barbara Mair, Simon Wöhrle, Melanie Wurm, Nikolai Mischerikow, Michael J. Roy, Gerd Bader, Peter Greb, Géraldine Garavel, Emelyne Diers, Ross McLennan, Claire Whitworth, Vesna Vetma, Klaus Rumpel, Maximilian Scharnweber, Julian E. Fuchs, Thomas Gerstberger, Yunhai Cui, Gabriela Gremel, Paolo Chetta, Stefan Hopf, Nicole Budano, Joerg Rinnenthal, Gerhard Gmaschitz, Moriz Mayer, Manfred Koegl, Alessio Ciulli, Harald Weinstabl & William Farnaby

Nat. Commun. 2022, 13 (1), 5969.

doi: 10.1038/s41467-022-33430-6

12. Discovery of Soticlestat, a Potent and Selective Inhibitor for Cholesterol 24-Hydroxylase (CH24H)

Tatsuki Koike, Masato Yoshikawa, Haruhi Kamisaki Ando, William Farnaby, Toshiya Nishi, Etsorou Watanabe, Jason Yano, Maki Miyamoto, Shigeru Kondo, Tsuyoshi Ishi, Takanobu Kuroita

J Med Chem 2021 64(16):12228-12244.

doi: 10.1021/acs.jmedchem.1c00864

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

William Farnaby, Manfred Koegl, Darryl B. McConnell, Alessio Ciulli

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

doi: 10.1016/j.coph.2021.02.009

10. Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice

Toshiya Nishi, Shinichi Kondo, Maki Miyamoto, Sayuri Watanabe, Shigeo Hasegawa, Shigeru Kondo, Jason Yano, Etsurou Watanabe, Tsuyoshi Ishi, Masato Yoshikawa, Haruhi Kamisaki Ando, William Farnaby, Shinji Fujimoto, Eiji Sunahara, Momoko Ohori, Matthew J. During, Takanobu Kuroita & Tatsuki Koike

Scientific Reports 2020, 10, 17081

doi: 10.1038/s41598-020-74036-6

9. Protein degradation for drug discovery. [Editorial]

Alessio Ciulli & William Farnaby

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

doi: 10.1016/j.ddtec.2019.04.002

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

William Farnaby*, Manfred Koegl*, Michael J. Roy, Claire Whitworth, Emelyne Diers, Nicole Trainor, David Zollman, Steffen Steurer, Jale Karolyi-Oezguer, Carina Riedmueller, Teresa Gmaschitz, Johannes Wachter, Christian Dank, Michael Galant, Bernadette Sharps, Klaus Rumpel, Elisabeth Traxler, Thomas Gerstberger, Renate Schnitzer, Oliver Petermann, Peter Greb, Harald Weinstabl, Gerd Bader, Andreas Zoephel, Alexander Weiss-Puxbaum, Katharina Ehrenhöfer-Wölfer, Simon Wöhrle, Guido Boehmelt, Joerg Rinnenthal, Heribert Arnhof, Nicola Wiechens, Meng-Ying Wu, Tom Owen-Hughes, Peter Ettmayer, Mark Pearson, Darryl B. McConnell & Alessio Ciulli

*contributed equally

Nat Chem Biol 2019, 15 (7), 672–680.

doi: 10.1038/s41589-019-0294-6

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

Michael J. Roy, Sandra Winkler, Scott J. Hughes, Claire Whitworth, Michael Galant, William Farnaby, Klaus Rumpel, Alessio Ciulli

6. Identification of compounds acting as negative allosteric modulators of the LPA1 receptor

Jonathan Ellery, Louise Dickson, Toni Cheung, Loredana Ciuclan, Peter Bunyard, Stephen Mack, William J Buffham, William Farnaby, Philip Mitchell, Daniel Brown, Richard Isaacs, Matt Barnes

Eur J Pharmacol 2018 833, 8-15.

doi: 10.1016/j.ejphar.2018.05.040

5. Modular synthesis of thirty lead-like scaffolds suitable for CNS drug discovery

Joan Mayol-Llinas, William Farnaby, Adam Nelson

Chem. Commun. 2017, 53, 12345-12348

doi: 10.1039/C7CC06078E

4. Assessment of the Target Engagement and D-Serine Biomarker Profiles of the D-Amino Acid Oxidase Inhibitors Sodium Benzoate and PGM030756

Eimear Howley, Michael Bestwick, Rosa Fradley, Helen Harrison, Mathew Leveridge, Kengo Okada, Charlotte Fieldhouse, Will Farnaby, Hannah Canning, Andy P Sykes, Kevin Merchant, Katherine Hazel, Catrina Kerr, Natasha Kinsella, Louise Walsh, David G Livermore, Isaac Hoffman, Jonathan Ellery, Phillip Mitchell, Toshal Patel, Mark Carlton, Matt Barnes, David J Miller

Neurochem Res 2017, 42, 3279-3288.

doi: 10.1007/s11064-017-2367-9

3. Assessing molecular scaffolds for CNS drug discovery

Joan Mayol-Llinas, Adam Nelson, William Farnaby, Andrew Ayscough

Drug Discov Today 2017, 22, 965-969.

doi: 10.1016/j.drudis.2017.01.008

2. Synthesis of (−)-(S,S)-clemastine by Invertive N → C Aryl Migration in a Lithiated Carbamate

Anne M. Fournier,  Robert A. Brown, William Farnaby, Hideki Miyatake-Ondozabal and  Jonathan Clayden

Org. Lett. 2010, 12, 10, 2222–2225

doi: 10.1021/ol100627c

1. N to C Aryl Migration in Lithiated Carbamates: α-Arylation of Benzylic Alcohols

Jonathan Clayden, William Farnaby, Damian M. Grainger, Ulrich Hennecke, Michele Mancinelli ,Daniel J. Tetlow, Ian H. Hillier and Mark A. Vincent

J Am Chem Soc 2009, 131, 3410-3411.

doi: 10.1021/ja808959e

Patents

(Several have been granted in varying territories; for simplicity initial applications are shown only)

1. KRAS Degrading compounds comprising annulated 2-amino-3-cyano thiophenes WO2023099620 (2023)

2. Proteolysis targeting chimera (Protacs) as degraders of SMARCA2 and/or SMARCA4. WO2020078933 (2020)

3. 3-Substituted 2-aminoazaindole derivatives as GPR43 agonists and positive allosteric modulators and their preparation. WO2015198045 (2015).

4. Preparation of 1,3-substituted 2-aminoindole derivatives and analogues useful in the treatment or prevention of diabetes mellitus, obesity and inflammatory bowel disease. WO2015198046 (2015).

5. Preparation of amide derivatives as lysophosphatidic acid receptor antagonists. WO2015025164 (2015).

6. Preparation of pyridine and pyrimidine derivatives as cholesterol 24 hydroxylase inhibitors. WO2014163161 (2014).

7. Pyridazinones as DAAO enzyme inhibitors. WO2014096757 (2014)

8. Pyridazinone compounds and their use as DAAO inhibitors. WO2013027000 (2013).

9. Preparation of substituted hydroxypiperidines as cholesterol 24-hydroxylase inhibitors. US20130090341 (2013).

10. 5- or 6- substituted 3-hydroxy-2-(1H)-pyridinones as d-amino acid oxidase (DAAO) inhibitors in therapy of diseases such as schizophrenia, cognitive disorder and pain. WO2013004996 (2013).

11. Pyrimidinone compounds and their use. WO2013004995 (2013).