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Degraders (e.g.PROTAC® molecules, SNIPERs etc), are a new approach for the knockdown of target proteins within cells. Comprising binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, these hybrid molecules induce selective, proteasome-dependent degradation of target proteins and can be used to investigate downstream effects of protein knockdown or to interfere with specific signaling pathways.
PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
|Cat. No.||Product Name / Activity|
|7254||ARCC 4 New|
|Potent and selective androgen receptor PROTAC®|
|7256||ARV 771 New|
|Potent BET bromodomain PROTAC®; also degrades BRD-tagged chimeric antigen receptors (CAR) in T cells|
|(+)-JQ1 based PROTAC® with selectivity for BRD4|
|7319||BRD PHOTAC-I-3 New|
|Photoswitchable BET bromodomain Degrader (PHOTAC)|
|Selective Cdk6 Degrader (PROTAC®)|
|Selective Cdk4/6 Degrader (PROTAC®)|
|Selective Cdk4 Degrader (PROTAC®)|
|Homo-PROTAC for self-degradation of pVHL30|
|7219||CRBN PROTAC® 14a|
|Cereblon Degrader (PROTAC®)|
|Potent and selective cereblon Degrader (PROTAC®); cell-permeable|
|(+)-JQ1 based Degrader (PROTAC®) targeting BET bromodomains, active in vivo|
|Potent and selective (+)-JQ1 based Degrader (PROTAC®) targeting BET bromodomains, active in vivo|
|Potent and selective BRD9 Degrader (PROTAC®)|
|Potent BRD9 Degrader (PROTAC®)|
|Potent and selective BTK Degrader (PROTAC®)|
|TRIM24 Degrader (PROTAC®)|
|7258||Gefitinib-based PROTAC® 3 New|
|Potent EGFR PROTAC®|
|7265||GMB 475 New|
|BCR-ABL1 kinase PROTAC®|
|7395||MS 154 New|
|Potent and selective cereblon-recruiting Degrader (PROTAC®) of mutant EGFR|
|7397||MS 39 New|
|Potent and selective VHL-recruiting Degrader (PROTAC®) of mutant EGFR|
|(+)-JQ1 based Degrader (PROTAC®) that selectively degrades BRD4|
|SRC-1 peptide-based PROTAC®; active in vivo|
|Potent and selective p38α and p38β Degrader (PROTAC®); active in vivo|
|Selective EGFR PROTAC®|
|Potent EGFR PROTAC®; also degrades HER2|
|7266||SJF 8240 New|
|c-MET PROTAC®; also degrades exon-14-deleted c-MET|
|Potent and selective p38α PROTAC®|
|Potent and selective p38δ PROTAC®|
|Potent and selective ERα Degrader (SNIPER)|
|7259||TBK1 PROTAC® 3i New|
|Potent TANK-binding kinase 1 (TBK1) PROTAC®|
|6532||THAL SNS 032|
|Potent and selective Cdk9 Degrader (PROTAC®)|
|Multikinase Degrader (PROTAC®)|
|Selective ALK Degrader (PROTAC®)|
|Selective ALK Degrader (PROTAC®)|
|Potent and selective BRD7/9 Degrader (PROTAC®)|
|Selective peptide-based β-catenin Degrader (PROTAC®)|
|Potent and selective BRD4 Degrader (PROTAC®)|
|Cat. No.||Product Name / Activity|
|7255||ARCC 4 negative control New|
|Negative control for ARCC 4 (Cat. No. 7254)|
|Negative control for BSJ-03-123 (Cat. No. 6921)|
|6155||cis MZ 1|
|Negative Control for MZ 1 (Cat. No. 6154)|
|Negative control for VZ 185 (Cat. No. 6936)|
|Negative Control for CM 11 (Cat. No. 6416)|
|7396||MS 154N New|
|Negative control for MS 154 (Cat No. 7395)|
|7398||MS 39N New|
|Negative control for MS 39 (Cat. No. 7397)|
|7260||TBK1 control PROTAC® 4 New|
|Negative control for TBK1 PROTAC® 3i (Cat. No. 7259)|
|Negative control for TL 13-112 (Cat. No. 6745)|
|Negative control for TL 13-12 (Cat. No. 6744)|
|Negative control for TL 12-186 (Cat. No. 6524)|
Degraders (e.g.PROTAC® molecules, SNIPERs etc), are a useful approach for the knockdown of target proteins within cells. Comprising binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, these hybrid molecules induce selective, proteasome-dependent degradation of target proteins and can be used to investigate downstream effects of protein knockdown or to interfere with specific signaling pathways. The methodology provides an attractive alternative to RNAi methods and have several advantages including:
Figure 1: Schematic showing the catalytic mode of action of heterobifunctional degrader molecules. Degraders initiate the formation of a ternary complex between an E3 ubiquitin ligase and a target protein which results in polyubiquitination of the target protein, its recognition by the proteasome and subsequent degradation. Degraders act catalytically by repeatedly engaging and directing the ubiquitination of target molecules.
Adapted from Tinworth et al. (2016) MedChemComm 7 2206.
Another interesting feature of small molecule Degraders is their ability to confer additional selectivity, compared to the profile of the target protein ligand used. This is exemplified by AT 1 (Cat. No. 6356), which selectively degrades BRD4, whereas the target protein ligand component of AT 1, (+)- JQ1 (Cat. No. 4499), inhibits the closely related bromodomains of multiple BET family proteins.
Degraders are pharmacologically characterized by their DC50 and DMax values. These values can be used as a guide for the appropriate starting concentrations to use for your experiment. The DC50 is analogous to traditional IC50 values and is the concentration of Degrader at which 50% of the target protein is degraded. The DMax is the maximum level of degradation achievable.
An important factor to consider when using these products is the timescale required for maximum efficacy. This depends on the individual Degrader used; customers are referred to the references provided for each product for guidance. Another consideration is the 'hook effect', which leads to reduced degradation efficiency when high concentrations of compound are applied to cells. This is due to the formation of binary complexes, that compete with formation of the ternary complexes (E3 ligase-Degrader-target protein) required to achieve degradation. In general, very low concentrations of Degrader are required to achieve effective knock down.
Tocris offers the following scientific literature for Active Degraders to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
This brochure highlights the tools and services available from Bio-Techne to support Targeted Protein Degradation research, including:
Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.
Adapted from the 2015 Cancer Product Guide Edition 3, this poster summarizes the main epigenetic targets in cancer. The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets.
Degraders (e.g. PROTACs) are bifunctional small molecules, that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. They consist of three covalently linked components: an E3 ubiquitin ligase ligand, a linker and a ligand for the target protein of interest. Authored in-house, this poster outlines the generation of a toolbox of building blocks for the development of Degraders. The characteristics and selection of each of these components are discussed. Presented at EFMC 2018, Ljubljana, Slovenia