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E3 ligase ligands bind ubiquitin ligases such as cereblon and von Hippel-Lindau (VHL) in degrader design. In a degrader, they anchor the ligase end of the molecule. E3 ubiquitin ligases transfer ubiquitin to substrate proteins and mark them for degradation by the proteasome. Thalidomide and its analogs bind cereblon (CRBN), a substrate receptor of a cullin-based E3 ligase complex identified as their direct target in 2010. The category includes cereblon ligands such as thalidomide fluoride and TD-106, and VHL ligands such as VL285 and VH032-cyclopropane-F. These ligands are used to build proteolysis-targeting chimeras (PROTACs) and to study how ligases are recruited to new substrates.
KLHDC2-IN-1 is a ligand that specifically targets the ubiquitin E3 ligase KLHDC2, exhibiting a dissociation constant (Kd) of 160 nM. This compound facilitates the development of PROTACs, which are designed to induce degradation of BRD4 in cellular environments. Its application in cellular research underscores its potential utility in studying protein degradation mechanisms and therapeutic strategies targeting BRD4-related pathways.
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E3 ligase Ligand 58 is a selective ligand for E3 ligases, facilitating the synthesis of proteolysis-targeting chimeras (PROTACs). This compound plays a critical role in targeted protein degradation, enabling researchers to explore cellular mechanisms and therapeutic applications. E3 ligase Ligand 58 serves as a valuable tool in drug development and biological research focused on post-translational modifications.
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CYCA-117-70 is a ligand for DCAF1, exhibiting a binding affinity (KD) of 70 μM. It serves as an effective chemical handle for the development of proteolysis-targeting chimeras (PROTACs) that recruit DCAF1. This compound is valuable in research aiming to modulate protein degradation pathways, providing insights into cellular regulation and potential therapeutic applications.
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CRBN ligand-17 is an E3 ubiquitin ligase ligand that targets the cereblon (CRBN) substrate recognition domain. This compound is essential for the design and synthesis of PROTACs (proteolysis-targeting chimeras), which facilitate targeted protein degradation. Its application in research includes studying protein regulation mechanisms and investigating therapeutic strategies for various diseases.
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Deoxy-thalidomide-OMe is an E3 ligase ligand that plays a crucial role in targeted protein degradation mechanisms. This compound is utilized in the synthesis of PROTAC LRRK2 Degrader-4, facilitating research in the modulation of LRRK2 activity, which has implications in neurodegenerative diseases. Its ability to selectively engage with E3 ligases makes it a valuable tool for advancing studies in protein homeostasis and therapeutic development.
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(S,R,R)-VH032 is a selective VHL ligand that facilitates targeted protein degradation through its interaction with the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. This compound serves as a crucial building block in the synthesis of PROTACs, specifically enabling the development of NCOA4 degrader-1. Its application in research highlights its potential for advancing studies in targeted protein degradation and therapeutic intervention strategies.
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N-Demethylonalespib is an effective ligand for E3 ligase, playing a crucial role in ubiquitination pathways. This compound is instrumental in the synthesis of DDO3602, facilitating research into protein degradation and cellular regulation. Its application in cellular biology makes it a valuable tool for investigating E3 ligase-targeted therapies.
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RA183 is a selective ligand for E3 ligases, facilitating the development of proteolysis-targeting chimeras (PROTACs). This compound enables the targeted degradation of specific proteins by harnessing the ubiquitin-proteasome system, making it a valuable tool in chemical biology and drug discovery. RA183 can be utilized in various research applications aimed at elucidating protein function and developing innovative therapeutic strategies.
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(S,R,S)-AHPC-Ala is a ligand for E3 ubiquitin ligases, facilitating targeted protein degradation via the ubiquitin-proteasome pathway. This compound is instrumental in the synthesis of PROTAC SMARCA2/4-degrader-23, which is utilized in studies focused on the modulation of the SMARCA2 and SMARCA4 proteins. Its applications encompass research in cancer biology and therapeutic development, contributing to the advancement of targeted therapies.
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Arg12 is a 12-amino acid peptide sequence that functions as a ligand for E3 ubiquitin ligases. This compound is valuable for the synthesis of PROTACs, including the PROTAC PLK1 Degrader-2. Additionally, Arg12 possesses cell-penetrating properties, enabling effective delivery of larger molecules into cells, making it a useful tool in cellular research and therapeutic applications.
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Lenalidomide-4-aminomethyl is an E3 ligase ligand that specifically targets cereblon (CRBN), facilitating the recruitment of CRBN protein. This compound serves as an essential building block for the development of PROTAC molecules, enabling targeted protein degradation research. Its unique structural features make it a valuable tool for studying CRBN-mediated pathways and exploring therapeutic applications in cancer and other diseases.
Pomalidomide-piperazine is an active compound that serves as a critical building block for the synthesis of E3 ligands utilized in PROTAC (Proteolysis Targeting Chimeras) development. This compound facilitates targeted protein degradation by linking a protein of interest to an E3 ubiquitin ligase, promoting a novel approach to protein modulation. Its application is significant in drug discovery and therapeutic research focused on precision medicine.
E3 Ligase Ligand 31 is a specific ligand for E3 ubiquitin ligases, facilitating targeted protein degradation via the ubiquitin-proteasome system. This compound is instrumental in the synthesis of PTOTAC HSD17B13 degrader 1, making it a valuable tool for research in protein homeostasis and related therapeutic applications. Its utility in studying E3 ligase interactions offers insights into the modulation of protein levels in cellular and biochemical contexts.
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Cyclopropane-(S,R,S)-AHPC is a selective ligand for E3 ubiquitin ligases, which play a crucial role in ubiquitination processes affecting protein degradation and cellular regulation. This compound is valuable for research into post-translational modifications and protein interactions, enabling studies into cellular signaling pathways and disease mechanisms. Its ability to modulate E3 ligase activity makes it an essential tool for understanding protein homeostasis and developing targeted therapies.
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E3 Ligase Ligand 44 serves as an effective ligand for E3 ligases, facilitating the development of proteolysis-targeting chimeras (PROTACs) such as the AR Degrader-7. Its primary mechanism involves engaging E3 ligases to promote targeted protein degradation, enabling precise modulation of cellular pathways. This compound is useful in research focused on protein homeostasis, targeted therapy, and the exploration of novel therapeutic strategies in cancer and other diseases.
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E3 ligase Ligand 27 is a selective ligand targeting E3 ubiquitin ligases, facilitating the development of targeted protein degradation technologies. This compound is primarily utilized in the synthesis of the PROTAC BcI-2/BcI-xI Degrader-1, promoting the degradation of specific oncogenic proteins. Its application in research supports the investigation of novel therapeutic strategies in cancer treatment through the modulation of protein homeostasis.
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VH032 analogue-2 is a selective ligand for the E3 ubiquitin ligase von Hippel-Lindau (VHL), facilitating its recruitment in cellular processes. This compound effectively removes its protective group under acidic conditions, enabling its direct utilization in the synthesis of PROTAC (Proteolysis Targeting Chimeras) molecules. VH032 analogue-2 serves as a crucial intermediate for the development of VHL-based PROTACs, making it a valuable tool for research in targeted protein degradation and related fields.
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(S,S,S)-VH032 is a ligand for the E3 ubiquitin ligase von Hippel-Lindau (VHL), enabling targeted protein degradation through the formation of PROTACs. It plays a crucial role in the synthesis of PROTAC SGK3 degrader-2, facilitating the selective degradation of SGK3 and other target proteins. This compound is valuable for research in protein regulation and targeted therapeutic strategies.
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E3 Ligase Ligand 25 is a selective ligand for the E3 ubiquitin ligase, facilitating the synthesis of PROTACs, specifically the SOS1 degrader. This compound serves as a critical tool in studies aimed at targeted protein degradation, contributing to the advancement of therapeutic strategies in cancer and other diseases. Researchers can leverage E3 Ligase Ligand 25 to explore ubiquitin-mediated proteolysis and its implications in cellular regulation.
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Acepromazine-OTs is a ligand for the E3 ligase TRIM21, facilitating the recruitment of this protein in cellular contexts. It can be conjugated to target proteins via a linker to create PROTAC molecules, such as TrimTAC1. Acepromazine-OTs is valuable in research for deciphering protein degradation pathways and exploring targeted protein modulation approaches in therapeutic applications.
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E3 ligase Ligand 21 is a potent cereblon binder that facilitates the targeted degradation of Ikaros and Aiolos via the ubiquitin-proteasome pathway. This compound is valuable for research applications focusing on the modulation of transcription factors involved in hematologic malignancies and immune regulation. Its ability to selectively promote protein degradation makes it an important tool in the study of cellular homeostasis and targeted therapy development.
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E3 ligase Ligand 60 is a selective ligand for E3 ligase, facilitating the synthesis of JV8. This compound plays a pivotal role in targeted protein degradation research and investigation of E3 ligase-mediated pathways. It holds potential for advancing therapeutic strategies in various diseases by modulating protein levels through ubiquitin-proteasome pathways.
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Lenalidomide 5'-piperazine is an E3 ligase ligand that functions as a Cereblon (CRBN) recruitor. This compound can be utilized to create PROTAC (Proteolysis Targeting Chimeras) molecules by linking it to various target protein ligands through a suitable linker. Research applications include the study of targeted protein degradation and the modulation of cellular pathways related to tumorigenesis.
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VH032-CH2-Boc is a Boc-modified variant of VH032 that functions as a ligand for the E3 ubiquitin ligase von Hippel-Lindau (VHL) protein. This compound is designed to remove the protecting group under acidic conditions, making it suitable for direct incorporation into the synthesis of PROTAC molecules. VH032-CH2-Boc serves as a critical intermediate in the development of PROTACs targeting VHL, facilitating the targeted degradation of various proteins for research applications in drug discovery and cellular biology.
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SJ46411 is a potent ligand for KLHDC2, demonstrating a binding affinity with a Kd of approximately 260 nM as determined by isothermal titration calorimetry. Additional characterization includes SPR Kd of 0.5 μM and a TR-FRET IC50 of 3.9 μM, alongside a notable increase in thermal stability indicated by a ΔTm of 6.0 °C. This compound is valuable for research involving KLHDC2 interactions and can aid in elucidating its biological roles and potential as a therapeutic target.
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