Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs)
Abstract: Inhibition of more than one cancer‐related pathway by multi‐target agents is an emerging approach in modern anticancer drug discovery. Here, based on the well‐established synergy between histone deacetylase inhibitors (HDACi) and alkylating agents, we present the discovery of a series of alkylating HDACi using a pharmacophore‐linking strategy. For the parallel synthesis of the target compounds, we developed an efficient solid‐phase‐supported protocol using hydroxamic acids immobilized on resins (HAIRs) as stable and versatile building blocks for the preparation of functionalized HDACi. The most promising compound, 3 n, was significantly more active in apoptosis induction, activation of caspase 3/7, and formation of DNA damage (γ‐H2AX) than the sum of the activities of either active principle alone. Furthermore, to demonstrate the utility of our preloaded resins, the HAIR approach was successfully extended to the synthesis of a proof‐of‐concept proteolysis‐targeting chimera (PROTAC), which efficiently degrades histone deacetylases.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs) ; volume:59 ; number:50 ; year:2020 ; pages:22494-22499 ; extent:6
Angewandte Chemie / International edition. International edition ; 59, Heft 50 (2020), 22494-22499 (gesamt 6)
- Creator
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Sinatra, Laura
Bandolik, Jan Josef
Roatsch, Martin
Sönnichsen, Melf
Schoeder, Clara T.
Hamacher, Alexandra
Schöler, Andrea
Borkhardt, Arndt
Meiler, Jens
Bhatia, Sanil
Kassack, Matthias U.
Hansen, Finn Kristian
- DOI
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10.1002/anie.202006725
- URN
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urn:nbn:de:101:1-2022061412384873743616
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:23 AM CEST
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Associated
- Sinatra, Laura
- Bandolik, Jan Josef
- Roatsch, Martin
- Sönnichsen, Melf
- Schoeder, Clara T.
- Hamacher, Alexandra
- Schöler, Andrea
- Borkhardt, Arndt
- Meiler, Jens
- Bhatia, Sanil
- Kassack, Matthias U.
- Hansen, Finn Kristian
Other Objects (12)
Hydroxamic Acids Immobilized on Resins (HAIRs): Synthese von Dual‐Target‐HDAC‐Inhibitoren und HDAC‐PROTACs
Entwicklung von Klasse I/IIb Histondeacetylase (HDAC)-inhibitoren und HDAC-PROTACs
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Novel dual inhibitor targeting CDC25 and HDAC for treating triple-negative breast cancer
Balancing Histone Deacetylase (HDAC) Inhibition and Drug‐likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors
Epigenetische Regulierung und HDAC Inhibition von kolorektalen Karzinomen
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Hydroxamic Acids Immobilized on Resins (HAIRs): Synthese von Dual‐Target‐HDAC‐Inhibitoren und HDAC‐PROTACs
Entwicklung von Klasse I/IIb Histondeacetylase (HDAC)-inhibitoren und HDAC-PROTACs
Targeting aberrant histone acetylation in cancer: development of class I selective histone deacetylase (HDAC) inhibitors and dual HDAC/BET bromodomain inhibitors
Development of dual BET/HDAC inhibitors
Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC–MEF2 complexes
Balancing Histone Deacetylase (HDAC) Inhibition and Druglikeness : Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors
A DNA/HDAC dual‐targeting drug CY 190602 with significantly enhanced anticancer potency
Novel dual inhibitor targeting CDC25 and HDAC for treating triple-negative breast cancer
Balancing Histone Deacetylase (HDAC) Inhibition and Drug‐likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors
Epigenetische Regulierung und HDAC Inhibition von kolorektalen Karzinomen
CIK Cells and HDAC Inhibitors in Multiple Myeloma
HDAC inhibitors stimulate viral transcription by multiple mechanisms
Hydroxamic Acids Immobilized on Resins (HAIRs): Synthese von Dual‐Target‐HDAC‐Inhibitoren und HDAC‐PROTACs
Entwicklung von Klasse I/IIb Histondeacetylase (HDAC)-inhibitoren und HDAC-PROTACs
Targeting aberrant histone acetylation in cancer: development of class I selective histone deacetylase (HDAC) inhibitors and dual HDAC/BET bromodomain inhibitors
Development of dual BET/HDAC inhibitors
Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC–MEF2 complexes
Balancing Histone Deacetylase (HDAC) Inhibition and Druglikeness : Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors
A DNA/HDAC dual‐targeting drug CY 190602 with significantly enhanced anticancer potency
Novel dual inhibitor targeting CDC25 and HDAC for treating triple-negative breast cancer
Balancing Histone Deacetylase (HDAC) Inhibition and Drug‐likeness: Biological and Physicochemical Evaluation of Class I Selective HDAC Inhibitors
Epigenetische Regulierung und HDAC Inhibition von kolorektalen Karzinomen
CIK Cells and HDAC Inhibitors in Multiple Myeloma