PROTAC chemical probes for histone deacetylase enzymes

Urvashi Patel, Joshua P. Smalley and James T. Hodgkinson

RSC Chem. Biol., 2023, 4, 623
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Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design

Robert Kuchta, Christopher Heim, Alexander Herrmann, Samuel Maiwald, Yuen Lam Dora Ng, Izidor Sosič, Tim Keuler, Jan Krönke, Michael Gütschow, Marcus D. Hartmann and Christian Steinebach

RSC Chem. Biol., 2023, 4, 229
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Degrading the key component of the inflammasome: development of an NLRP3 PROTAC

Tim Keuler, Dominic Ferber, Jonas Engelhardt, Christian Steinebach, Nico Kirsch, Michael Marleaux, Günther Weindl, Matthias Geyer and Michael Gütschow

Chem. Commun., 2025, 61, 3001
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Development and Characterization of the First Selective Class IIb Histone Deacetylase Degraders

Shiyang Zhai, Irina Honin, Linda Schäker-Hübner, Maria Hanl, Lukas Jacobi, Finn Dressler, Dominika Ewa Pieńkowska, Philipp König, Jan Gerhartz, Rabea Voget, Gerd Bendas, Michael Gütschow, Felix Meissner, Bjoern B. Burckhardt, Radosław P. Nowak, Christian Steinebach and Finn K. Hansen

J. Med. Chem., 2025, 68, 13793
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Epigenetic therapy meets targeted protein degradation: HDAC-PROTACs in cancer treatment

Md Sadique Hussain, Liming Zhang, Amita Joshi Rana, Mudasir Maqbool, Sumel Ashique, Yumna Khan, Vikas Jakhmola, Ali Hanbashi, Wedad Mawkili and Gyas Khan

Future Medicinal Chemistry, 2025, 17, 1725
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Targeted Protein Degradation of Histone Deacetylases by Hydrophobically Tagged Inhibitors

Felix Feller and Finn K. Hansen

ACS Med. Chem. Lett., 2023, 14, 1863
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Tackling triple negative breast cancer with HDAC inhibitors: 6 is the isoform!

Anna Guadagni, Simona Barone, Antonella Ilenia Alfano, Sveva Pelliccia, Ivana Bello, Elisabetta Panza, Vincenzo Summa and Margherita Brindisi

European Journal of Medicinal Chemistry, 2024, 279, 116884
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Difluoromethyl-1,3,4-oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone Deacetylase 6

Beate König, Paris R. Watson, Nina Reßing, Abigail D. Cragin, Linda Schäker-Hübner, David W. Christianson and Finn K. Hansen

J. Med. Chem., 2023, 66, 13821
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Advances in designing ternary complexes: Integrating in-silico and biochemical methods for PROTAC optimisation in target protein degradation

Shareef Shaik, Prasanna Kumar Reddy Gayam, Manish Chaudhary, Gurvinder Singh and Aravinda Pai

Bioorganic Chemistry, 2024, 153, 107868
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Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel–Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1α Stabilizers

Lan Phuong Vu, Claudia J. Diehl, Ryan Casement, Adam G. Bond, Christian Steinebach, Nika Strašek, Aleša Bricelj, Andrej Perdih, Gregor Schnakenburg, Izidor Sosič, Alessio Ciulli and Michael Gütschow

J. Med. Chem., 2023, 66, 12776
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Chemical Versatility in Catalysis and Inhibition of the Class IIb Histone Deacetylases

David W. Christianson

Acc. Chem. Res., 2024, 57, 1135
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2-(Difluoromethyl)-1,3,4-oxadiazoles: The Future of Selective Histone Deacetylase 6 Modulation?

Beate König and Finn K. Hansen

ACS Pharmacol. Transl. Sci., 2024, 7, 899
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Back in Person: Frontiers in Medicinal Chemistry 2023

Matthias Gehringer, Felix Pape, María Méndez, Philipp Barbie, Andrea Unzue Lopez, Julien Lefranc, Franca‐Maria Klingler, Gerhard Hessler, Thierry Langer, Eleonora Diamanti and Matthias Schiedel

ChemMedChem, 2023, 18
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Perspectives and new aspects of histone deacetylase inhibitors in the therapy of CNS diseases

Bo Han, Mengfei Wang, Jiayi Li, Qiushi Chen, Niubing Sun, Xuezhi Yang and Qingwei Zhang

European Journal of Medicinal Chemistry, 2023, 258, 115613
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Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues

Marta Pichlak, Tomasz Sobierajski, Katarzyna M. Błażewska and Edyta Gendaszewska-Darmach

Journal of Enzyme Inhibition and Medicinal Chemistry, 2023, 38
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Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-oxadiazole Substrate Inhibitors and Modeling of Their Bioactivation Mechanism

Lena Ripa, Jenny Sandmark, Glyn Hughes, Igor Shamovsky, Anders Gunnarsson, Julia Johansson, Antonio Llinas, Mia Collins, Bomi Jung, Anna Novén, Nils Pemberton, Mickael Mogemark, Yao Xiong, Qing Li, Stefan Tångefjord, Margareta Ek and Annika Åstrand

J. Med. Chem., 2023, 66, 14188
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HDAC6 mediates tumorigenesis during mitosis and the development of targeted deactivating agents

Jie Peng, Hongyan Liu, Yujing Liu, Jingqian Liu, Qianlong Zhao, Wenjia Liu, Haoqian Niu, Haoyu Xue, Jie Sun and Jingde Wu

Bioorganic Chemistry, 2024, 153, 107818
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Monoselective Histone Deacetylase 6 PROTAC Degrader Shows In Vivo Tractability

Harsimran K. Garcha, Olasunkanmi O. Olaoye, Abootaleb Sedighi, Daniel Pölöske, Pearla Hariri, Wenlong Yu, Diaaeldin I. Abdallah, Richard Moriggl, Elvin D. de Araujo and Patrick T. Gunning

J. Med. Chem., 2025, 68, 6165
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Technologies of targeting histone deacetylase in drug discovery: Current progress and emerging prospects

Jinxiao Ru, Yuxi Wang, Zijia Li, Jiaxing Wang, Changyu Ren and Jifa Zhang

European Journal of Medicinal Chemistry, 2023, 261, 115800
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Slow-Binding and Covalent HDAC Inhibition: A New Paradigm?

Yasir S. Raouf and Carlos Moreno-Yruela

JACS Au, 2024, 4, 4148
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Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders

Jonathan van Eyll, Robert Prior, Sylvain Celanire, Ludo Van Den Bosch and Frederik Rombouts

Expert Opinion on Therapeutic Targets, 2024, 28, 719
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Development of the First-in-Class FEM1B-Recruiting Histone Deacetylase Degraders

Felix Feller, Irina Honin, Martina Miranda, Heiko Weber, Svenja Henze, Maria Hanl and Finn K. Hansen

J. Med. Chem., 2025, 68, 1824
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Pharmacological inhibition of HDAC6 suppresses NLRP3 inflammasome-mediated IL-1β release

Judith Bockstiegel, Silas L. Wurnig, Jonas Engelhardt, Jana Enns, Finn K. Hansen and Günther Weindl

Biochemical Pharmacology, 2023, 215, 115693
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Targeted protein degradation: advances in drug discovery and clinical practice

Guangcai Zhong, Xiaoyu Chang, Weilin Xie and Xiangxiang Zhou

Sig Transduct Target Ther, 2024, 9
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Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

Anton Frühauf, Martin Behringer and Franz-Josef Meyer-Almes

Molecules, 2023, 28, 5686
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Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups

Gustavo Salgado Pires, Heber Victor Tolomeu, Daniel Alencar Rodrigues, Lídia Moreira Lima, Carlos Alberto Manssour Fraga and Pedro de Sena Murteira Pinheiro

Pharmaceuticals, 2025, 18, 577
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Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells

Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski and Cyril Barinka

IJMS, 2023, 24, 4720
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Solid-Phase Synthesis of Cereblon-Recruiting Selective Histone Deacetylase 6 Degraders (HDAC6 PROTACs) with Antileukemic Activity

Laura Sinatra, Jing Yang, Julian Schliehe-Diecks, Niklas Dienstbier, Melina Vogt, Philip Gebing, Luisa M. Bachmann, Melf Sönnichsen, Thomas Lenz, Kai Stühler, Andrea Schöler, Arndt Borkhardt, Sanil Bhatia and Finn K. Hansen

J. Med. Chem., 2022, 65, 16860
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Cell biologist’s perspective: frontiers in the development of PROTAC-HDAC degraders

Alex Sobko

JSRT, 2022, 7, 40
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The Impact of Fluorination on the Design of Histone Deacetylase Inhibitors

Duong Tien Anh, Nguyen Hai Nam, Brigitte Kircher and Daniel Baecker

Molecules, 2023, 28, 1973
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Target Engagement Studies and Kinetic Live-Cell Degradation Assays Enable the Systematic Characterization of Histone Deacetylase 6 Degraders

Maria Hanl, Felix Feller, Irina Honin, Kathrin Tan, Martina Miranda, Linda Schäker-Hübner, Nico Bückreiß, Matthias Schiedel, Michael Gütschow, Gerd Bendas and Finn K. Hansen

ACS Pharmacol. Transl. Sci., 2025
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Comprehensive Mechanistic View of the Hydrolysis of Oxadiazole-Based Inhibitors by Histone Deacetylase 6 (HDAC6)

Lucia Motlová, Ivan Šnajdr, Zsófia Kutil, Erik Andris, Jakub Ptáček, Adéla Novotná, Zora Nováková, Barbora Havlínová, Werner Tueckmantel, Helena Dráberová, Pavel Majer, Mike Schutkowski, Alan Kozikowski, Lubomír Rulíšek and Cyril Bařinka

ACS Chem. Biol., 2023, 18, 1594
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